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{"sheet":"Table S8","index":0,"n_rows":213,"n_cols":18,"rows_kept":213,"cut":false,"hidden":false,"merged":[[212,0,212,14]]}
["All pathogenic CNV"]
["CNV overlapping ASD/ID genes or loci (stringent, > 30 kb)"]
["AGP ID","Gender","Family type","Ancestry","Stage","DNA source","Cytoband","Chr#:start-end (hg18)","Size","CNV type","RefSeq genes","Inheritance","Validation","Segregation in sibs","Clinical significance","CNV description","Phenotype","Parental phenotype"]
["16035_1571013001","M","Familial","European","Stage 2","CL","1q21.1","1:144482933-146325557",1842625,"Gain","ACP6, BCL9, CHD1L, FMO5, GJA5, GJA8, GPR89A, GPR89B, GPR89C, LOC728989, NBPF11, NBPF24, PDIA3P, PDZK1P1, PRKAB2","De novo","qPCR","(brother with Asperger syndrome, not tested)","Pathogenic","1q21.1 duplication syndrome","Autism (ADI-R ASD, ADOS autism), language delay (first words 48 mo, first phrases 66 mo), echolalic, functionally non-verbal, mild ID (Leiter at 14 y 11 mo: PIQ 68), normal vision and hearing, no dysmorphic features reported, no seizures","Both parents unaffected"]
["1952_301","M","Familial","Other ","Stage 1","CL","1q21.1","1:144500467-146336720",1836254,"Gain","ACP6, BCL9, CHD1L, FMO5, GJA5, GJA8, GPR89A, GPR89B, GPR89C, LOC728989, NBPF11, NBPF24, PDIA3P, PDZK1P1, PRKAB2","De novo","qPCR","not present in affected sister","Pathogenic","1q21.1 duplication syndrome","Diagnosed with Asperger syndrome, meets criteria for autism on ADI-R and ADOS, no language delay (first words 8 mo, first phrases 12 mo), walked at 16 mo; PPVT standard score 87, Raven NVIQ 97; hand-flapping and stereotyped body movements, no seizures, no other known disorders (AGRE ID: AU1301301).\nThe CNV is absent in the affected sister diagnosed with autism (meets criteria for autism both on ADI-R and ADOS), language delay (first words 30 mo, first phrases 42 mo), walked at 13 mo; PPVT standard score 68, Raven NVIQ 122; finger flicking, physical aggression toward noncaregivers/nonfamily members, no seizures, no other known disorders","Both parents unaffected"]
["8635_201","M","Familial (maternal cousin autism)","European","Stage 2","Blood","1q21.1","1:144500467-146377870",1877404,"Loss","ACP6, BCL9, CHD1L, FLJ39739, FMO5, GJA5, GJA8, GPR89A, GPR89B, GPR89C, LOC100130000, LOC728989, NBPF11, NBPF24, PDIA3P, PDZK1P1, PRKAB2","De novo","qPCR","(1 sister with epilepsy and unilateral deafness and 1 healthy sister, not tested)","Pathogenic","1q21.1 deletion syndrome","Autism on ADI-R and ADOS, comorbid OCD and ADHD; VIQ 93, PIQ 75, FSIQ 83; chronic ear infections; physical exam at 17 y, overweight (+4.7 SD, BMI 33.7), normal height, head circumference –1.5 SD, no epilepsy","Father seizures in infancy, mother healthy"]
["13135_1523","F","Unknown","European","Stage 1","Blood","1q21.1 ","1:144838594-146308287",1469694,"Gain","ACP6, BCL9, CHD1L, FMO5, GJA5, GJA8, GPR89B, GPR89C, LOC728989, NBPF11, NBPF24, PDIA3P, PDZK1P1, PRKAB2","De novo","qPCR","(1 brother with Asperger and dyspraxia, not tested)","Pathogenic","1q21.1 duplication syndrome","Autism (ADI-R and ADOS positive), language delay (first words 12 mo, first phrases 36 mo), low average IQ (Leiter PIQ 77), normal physical exam, no epilepsy","Mother unaffected"]
["4291_1","M","Familial","European","Stage 2","Blood","1q21.1","1:144967972-146317915",1349944,"Gain","ACP6, BCL9, CHD1L, FMO5, GJA5, GJA8, GPR89B, GPR89C, LOC728989, NBPF11, NBPF24, PDIA3P, PDZK1P1, PRKAB2","Maternal","qPCR","CNV not present in affected sib","Pathogenic","1q21.1 duplication syndrome","Autism (based on ADI-R), nonverbal after language regression at 33 mo, aggression; nuchal cord x3 and slow labor with fetal distress; multiple café-au-lait spots <5 cm, raised moles on scalp","Mother multiple café-au-lait spots; father Hashimoto's thyroiditis"]
["16074_1571042001","M","Sporadic","European","Stage 2","CL","2p16.3","2:50037898-50407550",369653,"Loss","NRXN1","Maternal","qPCR","(sib ADHD not tested)","Pathogenic","NRXN1 exonic deletion, maternal","Autism, moderate ID (Leiter Brief at 27 y: PIQ 42), 3 words, lost language at age 2 with fever-induced seizures, tall, encopresis. Subject also has a 22q11.2 duplication syndrome, paternal; two-hit example?","Father slow in school, mother unaffected"]
["14068_1180","M","Sporadic","European","Stage 1","Blood","2p16.3","2:50493827-50677835",184009,"Gain","NRXN1","De novo","qPCR","(1 healthy sister, not tested)","Pathogenic","NRXN1 intragenic duplication, predicted to result in a premature truncated protein","Autism (ADI-R and ADOS positive), neurodevelopmental delay with onset at 2 y (first words 9 mo, first phrases 36 mo, walked at 14 mo), functional language; normal IQ (WISC-III at 10 y: VIQ 97, PIQ 86, FSIQ 89); no dysmorphic features, no sleep problems, no epilepsy; brain MRI cortical atrophy","Both parents unaffected"]
["13017_223","F","Sporadic","European","Stage 1","Blood","2p16.3","2:50539877-50730546",190670,"Loss","NRXN1","De novo","qPCR","(not tested)","Pathogenic","NRXN1 exonic deletion","Autism on ADI-R and ADOS, severe ID (IQ <30), non-verbal, no dysmorphic features or associated medical conditions","No information"]
["13216_2383","M","Unknown","European","Stage 2","Blood","2p16.3","2:50968208-51214171",245964,"Loss","NRXN1","De novo","qPCR","(not tested)","Pathogenic","NRXN1 exonic deletion","Autism on ADI-R and ADOS, no language delay, verbal, borderline/low average IQ (PPVT-III VIQ 78, Leiter Brief PIQ 83), poor motor control, no dysmorphic features, no seizures","Broader autism phenotype absent in father, present in mother; father VIQ 87, mother VIQ 91 (PPVT)"]
["13153_1703","M","Sporadic","European","Stage 1","Blood","2p16.3","2:50990306-51222043",231738,"Loss","NRXN1","De novo","qPCR","(3 sibs, not tested)","Pathogenic","NRXN1 exonic deletion","Autism on ADI-R and ADOS, language delay, verbal, mild ID (WPPSI-R at 78 mo: 59 VIQ, 79 PIQ, 67 FSIQ), no dysmorphic features reported, no epilepsy, Wilms tumor (also present in one of his siblings, with developmental delay)","Broader autism phenotype absent in both parents; father VIQ 110, mother VIQ 106 (PPVT)"]
["13037_463","M","Sporadic","European","Stage 1","Blood","2p16.3","2:51002576-51157742",155167,"Loss","NRXN1","De novo","qPCR","(not tested)","Pathogenic","NRXN1 exonic deletion","Autism, mild ID, severe speech and language delay, no dysmorphic features","No information"]
["17027_1","M","Familial","European","Stage 2","Blood","2p16.3","2:51076611-51147600",70990,"Loss","NRXN1","Paternal","qPCR","CNV also present in affected brother","Pathogenic","NRXN1 exonic deletion","Autism (based on ADI-R and ADOS), language delay (first words 20 mo, first phrases 30 mo), walked at 15 mo, verbal, no ID (Raven NVIQ 87, PPVT VIQ 71); Vineland: Communication 101, Daily Living Skills 78, Socialization 64, Adaptive Behavior Composite 75; BMI 15.56, no dysmorphic features or other anomalies, normal neurological exam, no epilepsy","Both parents unaffected"]
["5353_3","F","Sporadic","European","Stage 1","Blood","6p21.32","6:33399849-33512042",112194,"Loss","CUTA, KIFC1, PHF1, SYNGAP1","De novo","qPCR","(2 non-ASD brothers and 1 non-ASD sister, not tested)","Pathogenic","SYNGAP1 exonic deletion","Autism (based on ADI-R and ADOS), language delay, very little spontaneous communication, below average non-verbal IQ (Leiter 36); EEG at age 1-2 y, possible seizure activity","No medical problems reported"]
["5386_3","M","Familial","Other ","Stage 1","Blood","6q25.3","6:156785155-158489874",1704720,"Loss","ARID1B, MIR3692, SERAC1, SNX9, SYNJ2, ZDHHC14","De novo","qPCR, Illumina 1M-duo for sib","1 brother with high functioning ASD (with none of the abnormalities present in his brother), no CNV","Pathogenic","ARID1B exonic deletion. Haploinsufficiency of ARID1B is associated with ID, corpus callosum abnormalities, severe speech impairment, and ASD","Autism (based on ADI‐R and ADOS), deafness (no words, 15‐20 signs), epilepsy, facial dysmorphism, agenesis of the corpus callosum, loss of white matter in the occipital lobes, undescended testes","Both are of Asian decent; mother healthy, father somewhat shy."]
["8446_201","M","Sporadic","European","Stage 2","Blood","7q11.23","7:72344426-73782113",1437688,"Loss","ABHD11, ABHD11-AS1, BAZ1B, BCL7B, CLDN3, CLDN4, CLIP2, DNAJC30, EIF4H, ELN, FKBP6, FZD9, GTF2I, GTF2IRD1, LAT2, LIMK1, MIR4284, MIR590, MLXIPL, NSUN5, RFC2, STX1A, TBL2, TRIM50, VPS37D, WBSCR22, WBSCR27, WBSCR28","De novo","qPCR","(not tested)","Pathogenic","Williams syndrome (7q11.23 deletion)","Autism (ADI-R, ADOS, and clinical diagnosis), language delay (first words 36 mo), verbal, no IQ available. No epilepsy, no dysmorphic features","Mother low IQ (WAIS III VIQ 52, PIQ 61, FSIQ 51), father untested"]
["13123_1403","F","Sporadic","European","Stage 1","Blood","9p24.3-p24.2","9:98998-3682923",3583926,"Loss","C9orf66, CBWD1, DMRT1, DMRT2, DMRT3, DOCK8, FLJ35024, FOXD4, KANK1, KCNV2, KIAA0020, RFX3, SMARCA2, VLDLR","De novo","qPCR","(not tested)","Pathogenic","Terminal 9p deletion, 3.58 Mb (14 genes). Two unrelated subjects with ID and PDD-NOS reported with overlapping deletions (Girirajan et al. 2011). The DECIPHER and ISCA databases also contain numerous cases with overlapping deletions of variable sizes.","Autism on ADI-R and ADOS, verbal, moderate/mild ID; normal birth but developed bilateral congenital diaphragmatic hernia; epilepsy, on anti-convulsants; asthma, no dysmorphic features","No information"]
["6259_3","M","Sporadic","European","Stage 2","Blood","9q34.3","9:139516033-140208462",692430,"Loss","ARRDC1, C9orf37, CACNA1B, EHMT1, FLJ40292, MIR602, MRPL41, PNPLA7, TUBBP5, WDR85, ZMYND19","De novo","qPCR","(1 healthy sister, no DNA)","Pathogenic","Kleefstra syndrome (9q34.3 deletion including EHMT1)","Autism, language delay (first words 54 mo, first phrases 60 mo), limited speech, severe ID, stiff and uncoordinated walk, head circumference at 2 y 9 mo –1.8 SD, no malformations, no epilepsy, normal brain CT scan","Both parents unaffected"]
["6325_3","M","Sporadic","European","Stage 2","Blood","11q13.3","11:70077507-70506315",428809,"Loss","MIR3664, SHANK2","De novo","qPCR","(no siblings)","Pathogenic","SHANK2 exonic deletion","Autism, moderate ID, congenital inguinal hernia, severe language delay, functional language, no dysmorphic features, normal neurological exam, hypermetropia, astigmatism, no epilepsy (reported in Leblond et al. 2012, subject AU038_3)","Both parents unaffected"]
["6319_3","M","Sporadic","European","Stage 1","Blood","11q13.3","11:70119917-70187872",67956,"Loss","SHANK2","De novo","qPCR","(1 healthy brother, no DNA)","Pathogenic","SHANK2 exonic deletion","PDD-NOS, language delay, functional language, mild ID, no epilepsy, hypermetropia, large and prominent ears, no other dysmorphic features, flat feet, normal brain MRI. Subject also has a 15q11.2 microdeletion between BP1 and BP2, paternal, of uncertain clinical significance (reported in Pinto et al. 2010; Leblond et al. 2012)","Both parents healthy"]
["5237_3","M","Sporadic","European","Stage 1","Blood","11q13.3-q13.4","11:70154458-70220632",66175,"Loss","SHANK2","De novo","qPCR, Agilent 1M","1 non-ASD sister, no CNV","Pathogenic","SHANK2 exonic deletion","Autism (based on ADI-R and ADOS), below average non-verbal IQ (Leiter 67), below average language (<1%ile), no epilepsy, 5th finger clinodactyly, several curled toes (reported in Pinto et al. 2010; Berkel et al. 2010)","Father adult ADHD, for which he takes medication; also has irritable bowel syndrome. Mother speech issues when younger and struggled with school, possible learning disability; issues with asthma, anxiety, and autoimmune skin issues (yeast, psoriasis); very social."]
["6240_4","M","Sporadic","European","Stage 1","Blood","11q24.2-q25","11:126633939-132060374",5426436,"Loss","ADAMTS15, ADAMTS8, APLP2, ARHGAP32, BARX2, C11orf45, ETS1, FLI1, KCNJ1, KCNJ5, NCRNA00167, NFRKB, NTM, OPCML, PRDM10, SNX19, ST14, TMEM45B, TP53AIP1, ZBTB44","De novo","qPCR","1 healthy sister, no CNV","Pathogenic","Chromosome 11q deletion syndrome (Jacobsen syndrome)","Autism, language delay (first words 3-4 y, first phrases 5 y), walked at 18 mo, functional language, mild ID (WISC-IV at 16 y: VIQ 45, PIQ 65, FSIQ 49), macrocephaly at birth required C-section; automutilations; at 11 y: macrocephaly (+3 SD), height +0.5 SD, weight +3 SD, minor dysmorphic facial features (low ears, flat nose and nasal bridge, high forehead), 1 café-au-lait spot on the back, normal neurological exam, no epilepsy; brain MRI at 3 y showed white matter abnormalities, no longer visible when the MRI was repeated at 11 y.","Both parents healthy"]
["20187_1464001","M","Sporadic","European","Stage 2","Blood","15q11.2-q13.1","15:18811937-26209270",7397334,"Gain","ATP10A, C15orf2, CXADRP2, CYFIP1, GABRA5, GABRB3, GABRG3, GOLGA6L1, GOLGA6L6, GOLGA8C, GOLGA8DP, GOLGA8E, GOLGA8IP, HBII-52-27, HBII-52-28, HBII-52-45, HBII-52-46, HERC2, HERC2P2, HERC2P3, HERC2P7, IPW, LOC646214, LOC727924, MAGEL2, MKRN3, NBEAP1, NDN, NF1P1, NIPA1, NIPA2, OCA2, OR4M2, OR4N3P, OR4N4, PAR-SN, PAR1, PAR4, PAR5, POTEB, PWRN1, PWRN2, REREP3, SNORD107, SNORD108, SNORD109A, SNORD109B, SNORD115-1, SNORD115-10, SNORD115-11, SNORD115-12, SNORD115-13, SNORD115-14, SNORD115-15, SNORD115-16, SNORD115-17, SNORD115-18, SNORD115-19, SNORD115-2, SNORD115-20, SNORD115-21, SNORD115-22, SNORD115-23, SNORD115-24, SNORD115-25, SNORD115-26, SNORD115-29, SNORD115-3, SNORD115-30, SNORD115-31, SNORD115-32, SNORD115-33, SNORD115-34, SNORD115-35, SNORD115-36, SNORD115-37, SNORD115-38, SNORD115-39, SNORD115-4, SNORD115-40, SNORD115-41, SNORD115-42, SNORD115-43, SNORD115-44, SNORD115-48, SNORD115-5, SNORD115-6, SNORD115-7, SNORD115-8, SNORD115-9, SNORD116-1, SNORD116-10, SNORD116-11, SNORD116-12, SNORD116-13, SNORD116-14, SNORD116-15, SNORD116-16, SNORD116-17, SNORD116-18, SNORD116-19, SNORD116-2, SNORD116-20, SNORD116-21, SNORD116-22, SNORD116-23, SNORD116-24, SNORD116-25, SNORD116-26, SNORD116-27, SNORD116-28, SNORD116-29, SNORD116-3, SNORD116-4, SNORD116-5, SNORD116-6, SNORD116-7, SNORD116-8, SNORD116-9, SNORD64, SNRPN, SNURF, TUBGCP5, UBE3A, WHAMML1","De novo","qPCR","(no siblings)","Pathogenic","15q11-q13 duplication syndrome, maternally derived","Autism on ADI-R and ADOS; regression, clear loss of language and skills, nonverbal; ID (could not complete Differential Abilities Scale due to low functioning); had 4-5 possible seizures without fever at age 3-4, an EEG was normal; chronic diarrhea; normal appearance, normal gait, head circumference 1.53 SD, no known congenital abnormalities","Father: SRS total 30; VIQ 119, PIQ 99, FSIQ 109; age at birth of child 40 y; BAPQ: total 2.86/2.53, aloof 3.25/2.75, language 1.83/2.17, rigid 3.50/2.67; PPVT 106; head circumference 58.7 cm, height 185.2 cm. Mother: SRS total 24; VIQ 99, PIQ 116, FSIQ 108; age at birth of child 41 y; BAPQ: total 2.06/2.36, aloof 1.67/2.00, language 1.83/2.42, rigid 2.67/2.67; PPVT 101; allergies, on SSRIs (but does not indicate what for)"]
["8630_201","M","Familial (cousin has ASD)","European","Stage 2","Blood","15q11.2-q13.1","15:19800798-26209270",6408473,"Gain","ATP10A, C15orf2, CYFIP1, GABRA5, GABRB3, GABRG3, GOLGA6L1, GOLGA8DP, GOLGA8E, GOLGA8IP, HBII-52-27, HBII-52-28, HBII-52-45, HBII-52-46, HERC2, HERC2P2, HERC2P7, IPW, LOC727924, MAGEL2, MKRN3, NDN, NIPA1, NIPA2, OCA2, OR4M2, OR4N3P, OR4N4, PAR-SN, PAR1, PAR4, PAR5, PWRN1, PWRN2, REREP3, SNORD107, SNORD108, SNORD109A, SNORD109B, SNORD115-1, SNORD115-10, SNORD115-11, SNORD115-12, SNORD115-13, SNORD115-14, SNORD115-15, SNORD115-16, SNORD115-17, SNORD115-18, SNORD115-19, SNORD115-2, SNORD115-20, SNORD115-21, SNORD115-22, SNORD115-23, SNORD115-24, SNORD115-25, SNORD115-26, SNORD115-29, SNORD115-3, SNORD115-30, SNORD115-31, SNORD115-32, SNORD115-33, SNORD115-34, SNORD115-35, SNORD115-36, SNORD115-37, SNORD115-38, SNORD115-39, SNORD115-4, SNORD115-40, SNORD115-41, SNORD115-42, SNORD115-43, SNORD115-44, SNORD115-48, SNORD115-5, SNORD115-6, SNORD115-7, SNORD115-8, SNORD115-9, SNORD116-1, SNORD116-10, SNORD116-11, SNORD116-12, SNORD116-13, SNORD116-14, SNORD116-15, SNORD116-16, SNORD116-17, SNORD116-18, SNORD116-19, SNORD116-2, SNORD116-20, SNORD116-21, SNORD116-22, SNORD116-23, SNORD116-24, SNORD116-25, SNORD116-26, SNORD116-27, SNORD116-28, SNORD116-29, SNORD116-3, SNORD116-4, SNORD116-5, SNORD116-6, SNORD116-7, SNORD116-8, SNORD116-9, SNORD64, SNRPN, SNURF, TUBGCP5, UBE3A, WHAMML1","De novo","qPCR","(no siblings)","Pathogenic","15q11-q13 duplication syndrome, paternally derived","Autism on ADI-R and ADOS, regression at 16 mo; average IQ (VIQ 80, PIQ 101, FSIQ 89); no dysmorphic features, no epilepsy","Both parents unaffected"]
["20069_1328001","M","Sporadic","European","Stage 2","Blood","15q11.2-q13.1","15:20203578-26209270",6005693,"Gain","ATP10A, C15orf2, CYFIP1, GABRA5, GABRB3, GABRG3, GOLGA6L1, GOLGA8DP, GOLGA8E, GOLGA8IP, HBII-52-27, HBII-52-28, HBII-52-45, HBII-52-46, HERC2, HERC2P2, HERC2P7, IPW, MAGEL2, MKRN3, NDN, NIPA1, NIPA2, OCA2, PAR-SN, PAR1, PAR4, PAR5, PWRN1, PWRN2, SNORD107, SNORD108, SNORD109A, SNORD109B, SNORD115-1, SNORD115-10, SNORD115-11, SNORD115-12, SNORD115-13, SNORD115-14, SNORD115-15, SNORD115-16, SNORD115-17, SNORD115-18, SNORD115-19, SNORD115-2, SNORD115-20, SNORD115-21, SNORD115-22, SNORD115-23, SNORD115-24, SNORD115-25, SNORD115-26, SNORD115-29, SNORD115-3, SNORD115-30, SNORD115-31, SNORD115-32, SNORD115-33, SNORD115-34, SNORD115-35, SNORD115-36, SNORD115-37, SNORD115-38, SNORD115-39, SNORD115-4, SNORD115-40, SNORD115-41, SNORD115-42, SNORD115-43, SNORD115-44, SNORD115-48, SNORD115-5, SNORD115-6, SNORD115-7, SNORD115-8, SNORD115-9, SNORD116-1, SNORD116-10, SNORD116-11, SNORD116-12, SNORD116-13, SNORD116-14, SNORD116-15, SNORD116-16, SNORD116-17, SNORD116-18, SNORD116-19, SNORD116-2, SNORD116-20, SNORD116-21, SNORD116-22, SNORD116-23, SNORD116-24, SNORD116-25, SNORD116-26, SNORD116-27, SNORD116-28, SNORD116-29, SNORD116-3, SNORD116-4, SNORD116-5, SNORD116-6, SNORD116-7, SNORD116-8, SNORD116-9, SNORD64, SNRPN, SNURF, TUBGCP5, UBE3A, WHAMML1","De novo","qPCR","(no siblings)","Pathogenic","15q11-q13 duplication syndrome, maternally derived","Autism on ADI-R and ADOS, delayed language, verbal, borderline IQ (72), unusual computational skills, anxiety, milk intolerance; no dysmorphic features, head circumference 97%ile (like his father), normal gait, no epilepsy, normal vision","Mother some anxiety symptoms, allergies, family history of depression; father healthy"]
["17035_1","F","Sporadic","European","Stage 2","Blood","15q11.2-q13.1","15:20274130-26120360",5846231,"Gain","ATP10A, C15orf2, CYFIP1, GABRA5, GABRB3, GABRG3, GOLGA6L1, GOLGA8E, GOLGA8IP, HBII-52-27, HBII-52-28, HBII-52-45, HBII-52-46, HERC2, HERC2P2, HERC2P7, IPW, MAGEL2, MKRN3, NDN, NIPA1, NIPA2, OCA2, PAR-SN, PAR1, PAR4, PAR5, PWRN1, PWRN2, SNORD107, SNORD108, SNORD109A, SNORD109B, SNORD115-1, SNORD115-10, SNORD115-11, SNORD115-12, SNORD115-13, SNORD115-14, SNORD115-15, SNORD115-16, SNORD115-17, SNORD115-18, SNORD115-19, SNORD115-2, SNORD115-20, SNORD115-21, SNORD115-22, SNORD115-23, SNORD115-24, SNORD115-25, SNORD115-26, SNORD115-29, SNORD115-3, SNORD115-30, SNORD115-31, SNORD115-32, SNORD115-33, SNORD115-34, SNORD115-35, SNORD115-36, SNORD115-37, SNORD115-38, SNORD115-39, SNORD115-4, SNORD115-40, SNORD115-41, SNORD115-42, SNORD115-43, SNORD115-44, SNORD115-48, SNORD115-5, SNORD115-6, SNORD115-7, SNORD115-8, SNORD115-9, SNORD116-1, SNORD116-10, SNORD116-11, SNORD116-12, SNORD116-13, SNORD116-14, SNORD116-15, SNORD116-16, SNORD116-17, SNORD116-18, SNORD116-19, SNORD116-2, SNORD116-20, SNORD116-21, SNORD116-22, SNORD116-23, SNORD116-24, SNORD116-25, SNORD116-26, SNORD116-27, SNORD116-28, SNORD116-29, SNORD116-3, SNORD116-4, SNORD116-5, SNORD116-6, SNORD116-7, SNORD116-8, SNORD116-9, SNORD64, SNRPN, SNURF, TUBGCP5, UBE3A, WHAMML1","De novo","qPCR","(not tested)","Pathogenic","15q11-q13 duplication syndrome, maternally derived","Asperger syndrome (ADI-R: ASD, ADOS: autism), ADHD, stuttering and cluttering, no language delay, verbal, average IQ (WISC IV: VIQ 111, PIQ 100, FSIQ 107), walked at 12 mo, no dysmorphic features or other anomalies, normal neurological exam, no epilepsy","Both parents unaffected"]
["8117_202","M","Familial","European","Stage 2","Blood","15q11.2-q13.1","15:21168391-26217954",5049564,"Gain","ATP10A, C15orf2, GABRA5, GABRB3, GABRG3, HBII-52-27, HBII-52-28, HBII-52-45, HBII-52-46, HERC2, IPW, MAGEL2, MKRN3, NDN, OCA2, PAR-SN, PAR1, PAR4, PAR5, PWRN1, PWRN2, SNORD107, SNORD108, SNORD109A, SNORD109B, SNORD115-1, SNORD115-10, SNORD115-11, SNORD115-12, SNORD115-13, SNORD115-14, SNORD115-15, SNORD115-16, SNORD115-17, SNORD115-18, SNORD115-19, SNORD115-2, SNORD115-20, SNORD115-21, SNORD115-22, SNORD115-23, SNORD115-24, SNORD115-25, SNORD115-26, SNORD115-29, SNORD115-3, SNORD115-30, SNORD115-31, SNORD115-32, SNORD115-33, SNORD115-34, SNORD115-35, SNORD115-36, SNORD115-37, SNORD115-38, SNORD115-39, SNORD115-4, SNORD115-40, SNORD115-41, SNORD115-42, SNORD115-43, SNORD115-44, SNORD115-48, SNORD115-5, SNORD115-6, SNORD115-7, SNORD115-8, SNORD115-9, SNORD116-1, SNORD116-10, SNORD116-11, SNORD116-12, SNORD116-13, SNORD116-14, SNORD116-15, SNORD116-16, SNORD116-17, SNORD116-18, SNORD116-19, SNORD116-2, SNORD116-20, SNORD116-21, SNORD116-22, SNORD116-23, SNORD116-24, SNORD116-25, SNORD116-26, SNORD116-27, SNORD116-28, SNORD116-29, SNORD116-3, SNORD116-4, SNORD116-5, SNORD116-6, SNORD116-7, SNORD116-8, SNORD116-9, SNORD64, SNRPN, SNURF, UBE3A","Maternal","qPCR","CNV also present in affected sib (19703), absent in unaffected brother (19706)","Pathogenic","15q11-q13 duplication syndrome, maternally derived","Autism (ADI-R and ADOS positive), no language delay, verbal; moderate ID (WISC-III: VIQ 50, PIQ 50, FSIQ 42)","N/A"]
["8741_201","F","Familial","Other ","Stage 2","Blood","15q11.2-q13.1","15:21168391-26315093",5146703,"Gain","ATP10A, C15orf2, GABRA5, GABRB3, GABRG3, GOLGA8F, GOLGA8G, HBII-52-27, HBII-52-28, HBII-52-45, HBII-52-46, HERC2, IPW, MAGEL2, MKRN3, NDN, OCA2, PAR-SN, PAR1, PAR4, PAR5, PWRN1, PWRN2, SNORD107, SNORD108, SNORD109A, SNORD109B, SNORD115-1, SNORD115-10, SNORD115-11, SNORD115-12, SNORD115-13, SNORD115-14, SNORD115-15, SNORD115-16, SNORD115-17, SNORD115-18, SNORD115-19, SNORD115-2, SNORD115-20, SNORD115-21, SNORD115-22, SNORD115-23, SNORD115-24, SNORD115-25, SNORD115-26, SNORD115-29, SNORD115-3, SNORD115-30, SNORD115-31, SNORD115-32, SNORD115-33, SNORD115-34, SNORD115-35, SNORD115-36, SNORD115-37, SNORD115-38, SNORD115-39, SNORD115-4, SNORD115-40, SNORD115-41, SNORD115-42, SNORD115-43, SNORD115-44, SNORD115-48, SNORD115-5, SNORD115-6, SNORD115-7, SNORD115-8, SNORD115-9, SNORD116-1, SNORD116-10, SNORD116-11, SNORD116-12, SNORD116-13, SNORD116-14, SNORD116-15, SNORD116-16, SNORD116-17, SNORD116-18, SNORD116-19, SNORD116-2, SNORD116-20, SNORD116-21, SNORD116-22, SNORD116-23, SNORD116-24, SNORD116-25, SNORD116-26, SNORD116-27, SNORD116-28, SNORD116-29, SNORD116-3, SNORD116-4, SNORD116-5, SNORD116-6, SNORD116-7, SNORD116-8, SNORD116-9, SNORD64, SNRPN, SNURF, UBE3A","Maternal","qPCR","CNV also present in brother with autism and in 1 sister with speech delay; absent in 3 unaffected sisters","Pathogenic","15q11-q13 duplication syndrome, maternally derived","Proband: autism on ADI-R, language delay, eating and sleeping difficulties, chronic ear infections; moderate ID (at 5 y: VIQ 51, PIQ 45, FSIQ 47); no epilepsy.\nThe duplication is also present in the affected brother (autism on ADI; language delay: first words 3 y, first sentences 4 y; at 11 y, receptive language skills in the mild severity range and expressive language skills in the average range; low average IQ: VIQ 89, PIQ 84, FSIQ 86; no epilepsy) and in 1 sister with speech delay (not screened for autism)","Mother carries a duplication of maternal origin; she has learning disability and autistic traits. Father healthy"]
["13050_593","M","Sporadic","European","Stage 1","Blood","15q11.2-q13.1","15:21190624-26203954",5013331,"Gain","ATP10A, C15orf2, GABRA5, GABRB3, GABRG3, HBII-52-27, HBII-52-28, HBII-52-45, HBII-52-46, HERC2, IPW, MAGEL2, MKRN3, NDN, OCA2, PAR-SN, PAR1, PAR4, PAR5, PWRN1, PWRN2, SNORD107, SNORD108, SNORD109A, SNORD109B, SNORD115-1, SNORD115-10, SNORD115-11, SNORD115-12, SNORD115-13, SNORD115-14, SNORD115-15, SNORD115-16, SNORD115-17, SNORD115-18, SNORD115-19, SNORD115-2, SNORD115-20, SNORD115-21, SNORD115-22, SNORD115-23, SNORD115-24, SNORD115-25, SNORD115-26, SNORD115-29, SNORD115-3, SNORD115-30, SNORD115-31, SNORD115-32, SNORD115-33, SNORD115-34, SNORD115-35, SNORD115-36, SNORD115-37, SNORD115-38, SNORD115-39, SNORD115-4, SNORD115-40, SNORD115-41, SNORD115-42, SNORD115-43, SNORD115-44, SNORD115-48, SNORD115-5, SNORD115-6, SNORD115-7, SNORD115-8, SNORD115-9, SNORD116-1, SNORD116-10, SNORD116-11, SNORD116-12, SNORD116-13, SNORD116-14, SNORD116-15, SNORD116-16, SNORD116-17, SNORD116-18, SNORD116-19, SNORD116-2, SNORD116-20, SNORD116-21, SNORD116-22, SNORD116-23, SNORD116-24, SNORD116-25, SNORD116-26, SNORD116-27, SNORD116-28, SNORD116-29, SNORD116-3, SNORD116-4, SNORD116-5, SNORD116-6, SNORD116-7, SNORD116-8, SNORD116-9, SNORD64, SNRPN, SNURF, UBE3A","De novo","qPCR","(not tested)","Pathogenic","15q11-q13 duplication syndrome, maternally derived","Autism on ADI-R and ADOS, language delay (first words 36 mo, first phrases 48 mo), verbal, mild ID; anoxia at birth due to cord around neck; EEG yielded inconclusive results (abnormalities in one hemisphere); asthma, no dysmorphic features. Family history of autism (nephew Asperger syndrome) and depression","No information"]
["1950_301","M","Familial","European","Stage 1","CL","15q13.1-q13.3","15:26762141-30436163",3674023,"Loss","APBA2, ARHGAP11B, CHRFAM7A, CHRNA7, DKFZP434L187, FAM189A1, FAM7A1, FAM7A2, FAM7A3, FAN1, KLF13, LOC100288637, LOC100289656, LOC646278, LOC653075, MIR211, MTMR10, NDNL2, OTUD7A, TJP1, TRPM1, WHAMML2","Maternal","Illumina 550K (Glessner et al. 2009)","(not tested)","Pathogenic","15q13.3 deletion syndrome","Autism on ADI-R and ASD on ADOS, non verbal, at 10 y 7 mo spoke 2-3 spontaneous word phrases, mostly echolalia; no IQ available (untestable by Raven), poor suck at birth, no epilepsy; no mention of any unusual physical features (AGRE ID: AU1024301)","No information"]
["16040_1571029001","M","Familial","European","Stage 2","CL","15q13.2-q13.3","15:28450423-30303265",1852843,"Loss","ARHGAP11B, CHRFAM7A, CHRNA7, FAM7A1, FAM7A2, FAN1, KLF13, LOC100288637, MIR211, MTMR10, OTUD7A, TRPM1","De novo","qPCR","(sib PDD-NOS, not tested)","Pathogenic","15q13.3 deletion syndrome","Autism (ADI-R and ADOS positive), no language delay (first words 13 mo, first phrases 18 mo), lost language, now verbal; ID (Vineland at 7 y 2 mo: Communication 35, Daily Living Skills 29, Socialization 51, Adaptive Behavior Composite 35)","Both parents unaffected"]
["14167_2720","M","Sporadic","European","Stage 1","Blood","15q13.2-q13.3","15:28705540-30436163",1730624,"Loss","ARHGAP11B, CHRNA7, FAN1, KLF13, LOC100288637, MIR211, MTMR10, OTUD7A, TRPM1","Paternal","qPCR","(no siblings)","Pathogenic","15q13.3 deletion syndrome","Autism, mild ID, phrase speech delay, no epilepsy, no dysmorphic features","Father unaffected"]
["18100_302","M","Familial","European","Stage 2","CL","15q13.2-q13.3","15:28714502-30303265",1588764,"Loss","ARHGAP11B, CHRNA7, FAN1, KLF13, LOC100288637, MIR211, MTMR10, OTUD7A, TRPM1","Paternal","qPCR","CNV also present in brother and sister with autism","Pathogenic","15q13.3 deletion syndrome","Autism (based on ADI-R and ADOS), language regression at 21 mo associated with illness (fever), single words at 42 mo, phrases at 54 mo; normal IQ (Raven NVIQ 129), PPVT standard score 77 (vocabulary functioning in the moderately low range), hand/finger mannerisms, toe-walking, sensory abnormalities, 1 febrile seizure at 3-4 y (AGRE ID: AU1802302). Brother and sister with autism (based on ADI-R and ADOS) also carry the 15q13.3 microdeletion","Father received speech and language therapy and had difficulty learning to read. Father's brother has kids with autism. Mother has hearing issues"]
["5537_3","M","Familial","European","Stage 2","CL","15q25.2-q25.3","15:82722026-83529838",807813,"Loss","ALPK3, DNM1P41, GOLGA6L5, LOC100506874, NMB, PDE8A, SCAND2, SEC11A, SLC28A1, UBE2Q2P1, WDR73, ZNF592, ZSCAN2","Maternal","Affy 500K, Illumina 2.5M, qPCR","1 sister (#61018) without social concerns without CNV, 1 brother (#61114) with ADHD diagnosed at 6 y and autism diagnosed at 13 y with CNV","Pathogenic","Distal 15q25.2 deletion syndrome. Novel microdeletion syndrome, involved in ID/ASD (Cooper et al. 2011)","Asperger syndrome, meets ADI-R criteria for autism, WISC-III FSIQ 103, advanced language skills, ADHD, obsessive behaviors, nocturnal generalized tonic-clonic seizure disorder resolved at age 8, Marfanoid looking, long palpebral fissures, long face with malar hypoplasia, high arched palate and dental crowding (prior to orthodontic work), long neck (reported in Marshall et al. 2008, subject NA0064-000)","Mother was very shy as child, depression at 40 y, physical exam: not dysmorphic, not marfanoid. "]
["14283_4060","M","Sporadic","European","Stage 1","Blood","16p13.11 ","16:14771033-16307313",1536281,"Loss","ABCC1, ABCC6, ABCC6P2, C16orf45, FOPNL, KIAA0430, MIR1972-1, MIR1972-2, MIR3179-1, MIR3179-2, MIR3179-3, MIR3180-1, MIR3180-2, MIR3180-3, MIR3180-4, MIR484, MPV17L, MYH11, NDE1, NOMO1, NOMO3, NPIP, NTAN1, PDXDC1, RRN3","Maternal","qPCR","(1 sister with learning disabilities, not tested)","Pathogenic","16p13.11 deletion syndrome","Autism on ADI-R, ASD on ADOS, no language delay (first words 12 mo, first phrases 18 mo), mild ID (WISC-III at 10 y 11 mo: VIQ 57, PIQ 51, FSIQ 52), myopia and astigmatism, no dysmorphic features, no epilepsy","Both parents unaffected"]
["3441_3","M","Sporadic","European","Stage 2","Blood","16p13.11","16:14808871-16215852",1406982,"Loss","ABCC1, ABCC6, ABCC6P2, C16orf45, FOPNL, KIAA0430, MIR1972-1, MIR1972-2, MIR3179-1, MIR3179-2, MIR3179-3, MIR3180-1, MIR3180-2, MIR3180-3, MIR3180-4, MIR484, MPV17L, MYH11, NDE1, NOMO1, NPIP, NTAN1, PDXDC1, RRN3","Paternal","qPCR","(not tested)","Pathogenic","16p13.11 deletion syndrome","High‐functioning autism, low-average IQ (WISC VIQ 82, PIQ 98, FSIQ 89), minor dysmorphic features, no epilepsy","Father healthy"]
["14412_5210","M","Sporadic","European","Stage 2","CL","16p13.11","16:14960247-16307313",1347067,"Loss","ABCC1, ABCC6, C16orf45, FOPNL, KIAA0430, MIR1972-1, MIR1972-2, MIR3179-1, MIR3179-2, MIR3179-3, MIR3180-4, MIR484, MPV17L, MYH11, NDE1, NOMO3, NTAN1, PDXDC1, RRN3","Maternal","qPCR, LR-PCR","(1 healthy sibling, not tested)","Pathogenic","16p13.11 deletion syndrome","Autism on ADI-R and ADOS, no language delay, verbal, average IQ (WISC-III at 9 y 2 mo: VIQ 101, PIQ 108, FSIQ 104), no dysmorphic features or other anomalies, neurological exam normal except for clumsiness, normal growth, no epilepsy. Negative family history.","Both parents unaffected"]
["2204_1","M","Sporadic","European","Stage 2","Blood","16p11.2","16:29466569-30147029",680461,"Loss","ALDOA, ASPHD1, BOLA2, BOLA2B, C16orf53, C16orf54, C16orf92, CDIPT, CORO1A, DOC2A, FAM57B, GDPD3, HIRIP3, INO80E, KCTD13, LOC100271831, LOC388242, LOC440354, LOC440356, LOC606724, LOC613037, LOC613038, MAPK3, MAZ, MVP, PPP4C, PRRT2, QPRT, SEZ6L2, SLC7A5P1, SLX1A, SLX1A-SULT1A3, SLX1B, SLX1B-SULT1A4, SPN, SULT1A3, SULT1A4, TAOK2, TBX6, TMEM219, YPEL3, ZG16","De novo","qPCR","(3 unaffected paternal half-siblings, no DNA)","Pathogenic","16p11.2 deletion syndrome","Atypical PDD/Asperger (autism on ADI-R, ASD on ADOS), verbal, Vineland Adaptive Behavior Composite score 50, overweight, no dysmorphic features, macrocephaly (+3.6 SD), myopia, no epilepsy, brain MRI normal","Both parents unaffected"]
["3544_3","M","Familial","European","Stage 2","Blood","16p11.2","16:29499858-30107306",607449,"Gain","ALDOA, ASPHD1, C16orf53, C16orf54, C16orf92, CDIPT, CORO1A, DOC2A, FAM57B, GDPD3, HIRIP3, INO80E, KCTD13, LOC100271831, LOC440356, MAPK3, MAZ, MVP, PPP4C, PRRT2, QPRT, SEZ6L2, SLC7A5P1, SPN, TAOK2, TBX6, TMEM219, YPEL3, ZG16","Maternal","no validation attempted (visual inspection)","(affected sib not tested, no DNA)","Pathogenic","16p11.2 duplication syndrome","ASD/PDD-NOS diagnosis, language delay, significant articulation and other language problems until at least age 8 y; average verbal and performance ability (British Picture Vocabulary Scale at 8 y 4 mo: VIQ 88). Slightly low tone in limbs, some motor coordination difficulties. Bowel problems, delayed continence, bloating, foul-smelling stools; investigations found no explanation. No regression, no seizures","No information"]
["20089_1391001","M","Sporadic","European","Stage 2","Blood","16p11.2","16:29502984-30107306",604323,"Loss","ALDOA, ASPHD1, C16orf53, C16orf54, C16orf92, CDIPT, CORO1A, DOC2A, FAM57B, GDPD3, HIRIP3, INO80E, KCTD13, LOC100271831, LOC440356, MAPK3, MAZ, MVP, PPP4C, PRRT2, QPRT, SEZ6L2, SLC7A5P1, SPN, TAOK2, TBX6, TMEM219, YPEL3, ZG16","De novo","qPCR","(unaffected younger dizygotic twins, not tested) ","Pathogenic","16p11.2 deletion syndrome","Autism on ADI-R and ADOS, no language delay, average IQ (90), normal appearance, normal head circumference, normal reflexes and gait, no epilepsy","Father: SRS total 18; VIQ 106, PIQ 112, FSIQ 109, age at birth of child 23 y; diagnostic testing for hyperactivity as a child; head circumference 55.3 cm, height 181 cm. Mother: SRS total 28; VIQ 103, PIQ 120, FSIQ 112, age at birth of child 20 y; on SSRIs for OCD, speech problems, reports delayed language as a child, allergies; head circumference 54.5 cm, height 166 cm "]
["5068_3","F","Familial","European","Stage 1","Blood","16p11.2 ","16:29502984-30127026",624043,"Loss","ALDOA, ASPHD1, BOLA2, BOLA2B, C16orf53, C16orf54, C16orf92, CDIPT, CORO1A, DOC2A, FAM57B, GDPD3, HIRIP3, INO80E, KCTD13, LOC100271831, LOC388242, LOC440356, LOC606724, LOC613038, MAPK3, MAZ, MVP, PPP4C, PRRT2, QPRT, SEZ6L2, SLC7A5P1, SLX1A, SLX1A-SULT1A3, SLX1B, SLX1B-SULT1A4, SPN, SULT1A3, SULT1A4, TAOK2, TBX6, TMEM219, YPEL3, ZG16","De novo","qPCR, Affy 500K (Marshall et al. 2008), Agilent 1M","1 brother with ASD, no CNV","Pathogenic","16p11.2 deletion syndrome, 50% mosaicism","Autism (based on ADI-R and ADOS), low average IQ, language delay, motor delay, neurologic assessment negative, adherent ear lobes (reported in Marshall et al. 2008; Fernandez et al. 2010; MM0088-003)","No information"]
["5262_4","M","Sporadic","European","Stage 1","CL","16p11.2 ","16:29502984-30210849",707866,"Gain","ALDOA, ASPHD1, BOLA2, BOLA2B, C16orf53, C16orf54, C16orf92, CDIPT, CORO1A, DOC2A, FAM57B, GDPD3, HIRIP3, INO80E, KCTD13, LOC100271831, LOC388242, LOC440354, LOC440356, LOC595101, LOC606724, LOC613037, LOC613038, MAPK3, MAZ, MVP, PPP4C, PRRT2, QPRT, SEZ6L2, SLC7A5P1, SLX1A, SLX1A-SULT1A3, SLX1B, SLX1B-SULT1A4, SPN, SULT1A3, SULT1A4, TAOK2, TBX6, TMEM219, YPEL3, ZG16","De novo","qPCR, Affy 500K (Marshall et al. 2008)","1 non-ASD brother and 1 non-ASD sister, no CNV in either","Pathogenic","16p11.2 duplication syndrome","Autism (based on ADI-R and ADOS), anxiety symptoms, below average non-verbal IQ (4%ile), below average language (<1%ile), cleft palate, congenital diaphragmatic hernia, epilepsy, recurrent ear infections, short stature, alopecia in left parietal area, hypertelorism, epicanthic folds, small ears with curved pinnae, smooth philtrum, 5th finger clinodactyly, hyperextensibility, scoliosis (reported in Marshall et al. 2008; Fernandez et al. 2010; SK0102-004)","Father unaffected, cleft palate. Mother learning difficulties in school with reading and spelling, repeated grade 5; SRS-Adult total raw score 35"]
["3211_3","M","Familial","European","Stage 1","Buccal","16p11.2","16:29502984-30127026",624043,"Gain","ALDOA, ASPHD1, BOLA2, BOLA2B, C16orf53, C16orf54, C16orf92, CDIPT, CORO1A, DOC2A, FAM57B, GDPD3, HIRIP3, INO80E, KCTD13, LOC100271831, LOC388242, LOC440356, LOC606724, LOC613038, MAPK3, MAZ, MVP, PPP4C, PRRT2, QPRT, SEZ6L2, SLC7A5P1, SLX1A, SLX1A-SULT1A3, SLX1B, SLX1B-SULT1A4, SPN, SULT1A3, SULT1A4, TAOK2, TBX6, TMEM219, YPEL3, ZG16","Maternal","qPCR","absent in 1 affected brother","Pathogenic","16p11.2 duplication syndrome","Autism, normal IQ, no language delay, height 97%ile, head circumference 50%ile, epicanthus, steepled palate, physical and neurological exam otherwise normal","No information"]
["5359_4","M","Sporadic","European","Stage 1","Blood","16p11.2 ","16:29554843-30195224",640382,"Loss","ALDOA, ASPHD1, BOLA2, BOLA2B, C16orf53, C16orf54, C16orf92, CDIPT, CORO1A, DOC2A, FAM57B, GDPD3, HIRIP3, INO80E, KCTD13, LOC100271831, LOC388242, LOC440354, LOC440356, LOC595101, LOC606724, LOC613037, LOC613038, MAPK3, MAZ, MVP, PPP4C, PRRT2, QPRT, SEZ6L2, SLX1A, SLX1A-SULT1A3, SLX1B, SLX1B-SULT1A4, SPN, SULT1A3, SULT1A4, TAOK2, TBX6, TMEM219, YPEL3, ZG16","De novo","qPCR, Affy 500K (Marshall et al. 2008), Agilent 1M","1 non-ASD sister, no CNV","Pathogenic","16p11.2 deletion syndrome","Autism (based on ADI-R and ADOS), delayed early language development but average language abilities, average IQ, anxiety disorder, sleep disturbance, obese, macrocephaly, dysmorphic features, 2-3 toe syndactyly, micropenis, hemivertebra (T10); normal brain CT (reported in Marshall et al. 2008; Fernandez et al. 2010; SK0019-004)","Father query Asperger syndrome, social issues when younger. SRS-Adult total raw score 84. The proband's mother reports that the proband's father has mental health issues. Mother papilary thyroid cancer, Graves disease."]
["20127_4014001","M","Sporadic","European","Stage 2","CL","16p11.2","16:29554843-30130862",576020,"Loss","ALDOA, ASPHD1, BOLA2, BOLA2B, C16orf53, C16orf54, C16orf92, CDIPT, CORO1A, DOC2A, FAM57B, GDPD3, HIRIP3, INO80E, KCTD13, LOC100271831, LOC388242, LOC440356, LOC606724, LOC613038, MAPK3, MAZ, MVP, PPP4C, PRRT2, QPRT, SEZ6L2, SLX1A, SLX1A-SULT1A3, SLX1B, SLX1B-SULT1A4, SPN, SULT1A3, SULT1A4, TAOK2, TBX6, TMEM219, YPEL3, ZG16","Paternal","qPCR","(no siblings)","Pathogenic","16p11.2 deletion syndrome","Autism on ADI-R and ADOS, delayed language, verbal, average IQ (92), allergies, anxiety, depression, no dysmorphic features, head circumference 99%ile, possible visual saccades during a smooth pursuit eye task, normal reflexes, mildly uncoordinated when walking and running, no seizures","Father: normal IQ (97); hearing problem present from childhood; learning difficulties with reading requiring tutoring"]
["4030_1","M","Familial","European","Stage 2","Blood","16p11.2","16:29554843-30107306",552464,"Gain","ALDOA, ASPHD1, C16orf53, C16orf54, C16orf92, CDIPT, CORO1A, DOC2A, FAM57B, GDPD3, HIRIP3, INO80E, KCTD13, LOC100271831, LOC440356, MAPK3, MAZ, MVP, PPP4C, PRRT2, QPRT, SEZ6L2, SPN, TAOK2, TBX6, TMEM219, YPEL3, ZG16","De novo","qPCR","CNV not present in affected sib","Pathogenic","16p11.2 duplication syndrome","Autism (based on medical history and ADI-R), verbal with history of expressive language delay, ADHD, depression; average IQ (Stanford–Binet at 4 y: FSIQ 90; WISC-III: VIQ 91, PIQ 80, FSIQ 84), history of recurring ear infections, sinus surgery at 4 y, no dysmorphic features","Mother speech delay until age 4, depression; father academic difficulties, aloof, poor social judgment"]
["3439_3","M","Sporadic","European","Stage 2","Blood","17p11.2","17:17156307-18262979",1106673,"Loss","ALKBH5, ATPAF2, C17orf39, DRG2, EVPLL, FLII, LLGL1, LRRC48, MED9, MIR33B, MYO15A, NT5M, PEMT, RAI1, RASD1, SHMT1, SMCR5, SMCR7, SMCR8, SREBF1, TOM1L2, TOP3A","De novo","qPCR","no CNV in unaffected sister","Pathogenic","Smith-Magenis syndrome (17p11.2 deletion including RAI1)","Atypical autism, mild ID (WAIS: VIQ 60, PIQ 64, FSIQ 57). Head circumference 50%ile; some mild dysmorphic features, including cupped ears; broad, prominent forehead; frontal hair upsweep (as his mother); mildly deep-set eyes, mild lax ligaments, hypotonic face, with drooling. Normal neurological exam, no epilepsy. Constipation (as in his mother) has been a concern","Both parents unaffected"]
["2211_1","F","Sporadic","European","Stage 2","Blood","17p11.2","17:17169258-20101517",2932260,"Loss","AKAP10, ALDH3A1, ALDH3A2, ALKBH5, ATPAF2, B9D1, C17orf39, CCDC144B, DRG2, EPN2, EVPLL, FAM106A, FAM18B1, FAM83G, FBXW10, FLII, FOXO3B, GRAP, GRAPL, LGALS9C, LLGL1, LOC220594, LOC339240, LRRC48, MAPK7, MED9, MFAP4, MIR1180, MIR33B, MYO15A, NT5M, PEMT, PRPSAP2, RAI1, RASD1, RNF112, SHMT1, SLC47A1, SLC47A2, SLC5A10, SMCR5, SMCR7, SMCR8, SNORA59A, SNORA59B, SPECC1, SREBF1, TBC1D28, TOM1L2, TOP3A, TRIM16L, ULK2, ZNF286B","De novo","qPCR","(2 unaffected siblings, no DNA)","Pathogenic","Smith-Magenis syndrome (17p11.2 deletion including RAI1)","Autism (meets ADI-R and ADOS criteria), language delay (first words 60 mo, first phrases 72 mo), verbal, developmental delay, Vineland Adaptive Behavior Composite score 38 (at 15 y), self-injurious behavior, hoards all types of things including food, impulsive, obsessive, head circumference +2 SD, slightly dysplastic ears, flattened nasal bridge, short hands with slightly tapered fingers, renal cyst; no mention of sleep disturbance in records","Both parents unaffected"]
["14315_4320","M","Sporadic","European","Stage 2","Blood","17q12","17:31621634-33323919",1702286,"Gain","AATF, ACACA, C17orf78, CCL3L1, CCL3L3, CCL4L1, CCL4L2, DDX52, DHRS11, DUSP14, GGNBP2, HNF1B, LHX1, LOC284100, MIR2909, MRM1, MYO19, PIGW, SYNRG, TADA2A, TBC1D3F, TBC1D3G, TBC1D3H, ZNHIT3","Maternal","qPCR","(older brother with language and motor delay, not sampled)","Pathogenic","17q12 duplication syndrome. 17q12 deletions are associated with renal cysts and diabetes syndrome, ID, ASD and schizophrenia (Moreno-De-Luca et al. 2010); duplications are associated with variable phenotype, including ID, renal problems and other malformations. Only 1 duplication published in a subject with autism (Brandt et al. 2012) but he was later found to carry a de novo nonsense mutation in SHANK3 (Soorya et al. 2013), so the contribution of the CNV to ASD is unclear","Autism on ADI-R and ADOS, language delay, verbal, performance DQ 93, verbal DQ 65, total DQ 84; normal birth parameters, no dysmorphic features or other congenital malformations, normal neurological exam, normal growth, no epilepsy. Older brother language and motor delay? (not evaluated)","Father epilepsy; mother major depression; she finished primary school\n"]
["3183_7","M","Familial","European","Stage 1","Buccal","22q11.21","22:17241748-19819918",2578171,"Loss","AIFM3, ARVCF, BCRP2, C22orf25, C22orf29, C22orf39, CDC45, CLDN5, CLTCL1, COMT, CRKL, DGCR10, DGCR11, DGCR14, DGCR2, DGCR5, DGCR6, DGCR6L, DGCR8, DGCR9, FLJ39582, GNB1L, GP1BB, GSC2, HIRA, KLHL22, LOC150185, LOC150197, LOC400891, LZTR1, MED15, MGC16703, MIR1286, MIR1306, MIR185, MIR3618, MRPL40, P2RX6, P2RX6P, PI4KA, PI4KAP1, POM121L4P, PRODH, RANBP1, RIMBP3, RTN4R, SCARF2, SEPT5, SEPT5-GP1BB, SERPIND1, SLC25A1, SLC7A4, SNAP29, TBX1, THAP7, TMEM191A, TMEM191B, TRMT2A, TSSK2, TXNRD2, UFD1L, ZDHHC8, ZNF74","De novo","qPCR","absent in 1 first degree cousin with autism","Pathogenic","22q11.2 deletion syndrome (DiGeorge/velocardiofacial syndrome)","Asperger syndrome (meets criteria for autism on ADI-R and ADOS), average range cognitive ability (British Picture Vocabulary Scale: VIQ 82, Raven's Standard Progressive Matrices: PIQ 74); complex language disorder with receptive and expressive difficulties. Early development included neonatal feeding difficulties, frequent diarrhea, failure to thrive, constant noisy respirations, recurrent chest and ear infections, walked at 18 mo; no epilepsy, no dysmorphic features noted, head circumference 93%ile, height 20%ile, squint; normal brain MRI and sleep EEG","Mother some evidence of obsessions and perfectionism, and anxiety; father some evidence of social emotional difficulties, and rigidity"]
["17015_1","M","Sporadic","European","Stage 2","CL","22q11.21","22:17257787-19795780",2537994,"Loss","AIFM3, ARVCF, BCRP2, C22orf25, C22orf29, C22orf39, CDC45, CLDN5, CLTCL1, COMT, CRKL, DGCR10, DGCR11, DGCR14, DGCR2, DGCR5, DGCR6, DGCR6L, DGCR8, DGCR9, FLJ39582, GNB1L, GP1BB, GSC2, HIRA, KLHL22, LOC150185, LOC150197, LOC400891, LZTR1, MED15, MGC16703, MIR1286, MIR1306, MIR185, MIR3618, MRPL40, P2RX6, P2RX6P, PI4KA, PI4KAP1, POM121L4P, PRODH, RANBP1, RIMBP3, RTN4R, SCARF2, SEPT5, SEPT5-GP1BB, SERPIND1, SLC25A1, SLC7A4, SNAP29, TBX1, THAP7, TMEM191A, TMEM191B, TRMT2A, TSSK2, TXNRD2, UFD1L, ZDHHC8, ZNF74","De novo","qPCR","(not tested)","Pathogenic","22q11.2 deletion syndrome (DiGeorge/velocardiofacial syndrome)","Autism (based on ADI-R and ADOS), language delay (first words 30 mo, phrases 60 mo), walked at 14 mo, verbal, no ID (Raven's Standard Progressive Matrices NVIQ 86, PPVT VIQ 72), normal weight (BMI 20.44), no dysmorphic features or other anomalies, normal neurological exam, no epilepsy","Both parents unaffected"]
["8627_201","M","Sporadic","European","Stage 2","Blood","22q11.21","22:17257787-19793730",2535944,"Gain","AIFM3, ARVCF, BCRP2, C22orf25, C22orf29, C22orf39, CDC45, CLDN5, CLTCL1, COMT, CRKL, DGCR10, DGCR11, DGCR14, DGCR2, DGCR5, DGCR6, DGCR6L, DGCR8, DGCR9, FLJ39582, GNB1L, GP1BB, GSC2, HIRA, KLHL22, LOC150185, LOC150197, LOC400891, LZTR1, MED15, MGC16703, MIR1286, MIR1306, MIR185, MIR3618, MRPL40, P2RX6, P2RX6P, PI4KA, PI4KAP1, POM121L4P, PRODH, RANBP1, RIMBP3, RTN4R, SCARF2, SEPT5, SEPT5-GP1BB, SERPIND1, SLC25A1, SLC7A4, SNAP29, TBX1, THAP7, TMEM191A, TMEM191B, TRMT2A, TSSK2, TXNRD2, UFD1L, ZDHHC8, ZNF74","De novo","qPCR","(2 healthy brothers, not tested)","Pathogenic","22q11.2 duplication syndrome","Autism on ADI-R and ADOS, bipolar disorder, born premature, normal IQ (VIQ 112, PIQ 109, FSIQ 112); physical exam at 19 y: head circumference >+2 SD, obesity (108 kg), height +1 SD, no epilepsy ","Father mood disorder, rigidity and social inappropriateness; mother healthy"]
["4271_1","M","Sporadic","European","Stage 2","Blood","22q11.21","22:17257787-19795780",2537994,"Gain","AIFM3, ARVCF, BCRP2, C22orf25, C22orf29, C22orf39, CDC45, CLDN5, CLTCL1, COMT, CRKL, DGCR10, DGCR11, DGCR14, DGCR2, DGCR5, DGCR6, DGCR6L, DGCR8, DGCR9, FLJ39582, GNB1L, GP1BB, GSC2, HIRA, KLHL22, LOC150185, LOC150197, LOC400891, LZTR1, MED15, MGC16703, MIR1286, MIR1306, MIR185, MIR3618, MRPL40, P2RX6, P2RX6P, PI4KA, PI4KAP1, POM121L4P, PRODH, RANBP1, RIMBP3, RTN4R, SCARF2, SEPT5, SEPT5-GP1BB, SERPIND1, SLC25A1, SLC7A4, SNAP29, TBX1, THAP7, TMEM191A, TMEM191B, TRMT2A, TSSK2, TXNRD2, UFD1L, ZDHHC8, ZNF74","De novo","qPCR","not present in unaffected sib","Pathogenic","22q11.2 duplication syndrome","Autism (based on medical history and ADI-R), ADHD, speech delay until 4 y, learning disability in written expression, normal to superior IQ (WISC 8 y: FSIQ 104; Differential Ability Scales 9 y: VCIQ 142, NVCIQ 152, SCIQ 154); normal CT and MRI, nonspecific EEG changes, seizures/staring spells/breath holding (reported in Griswold et al. 2012a; family 17164)","Mother attention deficit disorder, dyslexia, hypothyroidism; father unaffected"]
["16074_1571042001","M","Sporadic","European","Stage 2","CL","22q11.21","22:17257787-19793730",2535944,"Gain","AIFM3, ARVCF, BCRP2, C22orf25, C22orf29, C22orf39, CDC45, CLDN5, CLTCL1, COMT, CRKL, DGCR10, DGCR11, DGCR14, DGCR2, DGCR5, DGCR6, DGCR6L, DGCR8, DGCR9, FLJ39582, GNB1L, GP1BB, GSC2, HIRA, KLHL22, LOC150185, LOC150197, LOC400891, LZTR1, MED15, MGC16703, MIR1286, MIR1306, MIR185, MIR3618, MRPL40, P2RX6, P2RX6P, PI4KA, PI4KAP1, POM121L4P, PRODH, RANBP1, RIMBP3, RTN4R, SCARF2, SEPT5, SEPT5-GP1BB, SERPIND1, SLC25A1, SLC7A4, SNAP29, TBX1, THAP7, TMEM191A, TMEM191B, TRMT2A, TSSK2, TXNRD2, UFD1L, ZDHHC8, ZNF74","Paternal","qPCR","(sib ADHD not tested)","Pathogenic","22q11.2 duplication syndrome","Autism, moderate ID (Leiter Brief at 27 y: PIQ 42), 3 words, lost language at age 2 with fever-induced seizures, tall, encopresis. Subject also has an exonic NRXN1 deletion, maternal; two-hit example?","Father slow in school, mother unaffected"]
["3127_4","M","Familial","European","Stage 1","CL","22q11.21","22:17257787-19793730",2535944,"Gain","AIFM3, ARVCF, BCRP2, C22orf25, C22orf29, C22orf39, CDC45, CLDN5, CLTCL1, COMT, CRKL, DGCR10, DGCR11, DGCR14, DGCR2, DGCR5, DGCR6, DGCR6L, DGCR8, DGCR9, FLJ39582, GNB1L, GP1BB, GSC2, HIRA, KLHL22, LOC150185, LOC150197, LOC400891, LZTR1, MED15, MGC16703, MIR1286, MIR1306, MIR185, MIR3618, MRPL40, P2RX6, P2RX6P, PI4KA, PI4KAP1, POM121L4P, PRODH, RANBP1, RIMBP3, RTN4R, SCARF2, SEPT5, SEPT5-GP1BB, SERPIND1, SLC25A1, SLC7A4, SNAP29, TBX1, THAP7, TMEM191A, TMEM191B, TRMT2A, TSSK2, TXNRD2, UFD1L, ZDHHC8, ZNF74","Paternal","qPCR","present in 1 affected brother","Pathogenic","22q11.2 duplication syndrome","ASD, no language delay, articulation difficulties, limited and repetitive speech, normal IQ, severe learning difficulties, violent outbursts of aggression, abnormal EEG but no seizures, fine and gross motor problems, visuo-spatial difficulties, protruding tongue, several raised skin lesions (amelanotic and café-au-lait) on trunk, forehead and back of his neck (history of café au lait spots in the maternal family)","Father trouble reading and writing, problems with coordination, normal IQ"]
["5261_4","F","Familial","European","Stage 1","Blood","22q11.21","22:17257787-19795780",2537994,"Gain","AIFM3, ARVCF, BCRP2, C22orf25, C22orf29, C22orf39, CDC45, CLDN5, CLTCL1, COMT, CRKL, DGCR10, DGCR11, DGCR14, DGCR2, DGCR5, DGCR6, DGCR6L, DGCR8, DGCR9, FLJ39582, GNB1L, GP1BB, GSC2, HIRA, KLHL22, LOC150185, LOC150197, LOC400891, LZTR1, MED15, MGC16703, MIR1286, MIR1306, MIR185, MIR3618, MRPL40, P2RX6, P2RX6P, PI4KA, PI4KAP1, POM121L4P, PRODH, RANBP1, RIMBP3, RTN4R, SCARF2, SEPT5, SEPT5-GP1BB, SERPIND1, SLC25A1, SLC7A4, SNAP29, TBX1, THAP7, TMEM191A, TMEM191B, TRMT2A, TSSK2, TXNRD2, UFD1L, ZDHHC8, ZNF74","Paternal","qPCR, Illumina 1M-duo for sibs","1 maternal half-brother with autism and 1 non-ASD sister; no CNV in either","Pathogenic","22q11.2 duplication syndrome","Autism (based on ADI-R and ADOS), above average nonverbal IQ (96%ile), below average language (4%ile), no epilepsy, no dysmorphic features","Father unaffected"]
["2072_1","M","Familial","European","Stage 2","Blood","22q13.31-q13.33","22:45159185-49582267",4423083,"Loss","ACR, ADM2, ALG12, ARSA, BRD1, C22orf34, C22orf41, CELSR1, CERK, CHKB, CHKB-CPT1B, CPT1B, CRELD2, FAM116B, FAM19A5, FLJ46257, GRAMD4, HDAC10, IL17REL, KLHDC7B, LMF2, LOC100144603, LOC90834, MAPK11, MAPK12, MAPK8IP2, MIOX, MIR3201, MLC1, MOV10L1, NCAPH2, ODF3B, PANX2, PIM3, PLXNB2, PPP6R2, RABL2B, RPL23AP82, SBF1, SCO2, SELO, SHANK3, TBC1D22A, TRABD, TUBGCP6, TYMP, ZBED4","De novo (germinal mosaicism)","qPCR","present in 1 sister with autism (2072_2)","Pathogenic","Phelan-McDermid syndrome (22q13 deletion including SHANK3)","Autism (meets ADI-R and ADOS criteria), nonverbal, ID (Bayley Scale of Infant Development-II, mental developmental index 50, mental processing index 32), hyperactivity and attention deficits, treated with methylphenidate and risperidone, aggressiveness, self-injurious behavior, seizure disorder, normal head circumference, normal brain CT scan.\nDeletion also present in sister with autism (meets ADI-R and ADOS criteria), ID (unable to perform any of the tasks of the Differential Ability Scales), has only a few single words, normal EEG (reported in Sebat et al. 2007, subject 89-3524-100; Moessner et al. 2007, family 3524)","Both parents unaffected"]
["6130_4","F","Sporadic","European","Stage 2","Unknown (blood or CL)","22q13.32-q13.33","22:47996161-49512530",1516370,"Loss","ADM2, ALG12, ARSA, BRD1, C22orf34, C22orf41, CHKB, CHKB-CPT1B, CPT1B, CRELD2, FAM116B, HDAC10, IL17REL, KLHDC7B, LMF2, LOC100144603, LOC90834, MAPK11, MAPK12, MAPK8IP2, MIOX, MLC1, MOV10L1, NCAPH2, ODF3B, PANX2, PIM3, PLXNB2, PPP6R2, SBF1, SCO2, SELO, SHANK3, TRABD, TUBGCP6, TYMP, ZBED4","De novo","MLPA, qPCR","(1 healthy sister, no DNA)","Pathogenic","Phelan-McDermid syndrome (22q13 deletion including SHANK3)","Autism, severe ID, non verbal; neonatal hypotonia, gastro-esophageal reflux, regression at 20 mo, no dysmorphic features; developed hirsutism, obesity and leg dystonia in adolescence, with negative endocrine and neurological evaluations; brain MRI showed cortical atrophy, especially in posterior regions; no epilepsy","Both parents unaffected"]
["16079_1571066001","M","Sporadic","European","Stage 2","CL","22q13.33","22:49470371-49567383",97013,"Loss","ACR, RABL2B, RPL23AP82, SHANK3","De novo","qPCR","(2 unaffected siblings, not tested)","Pathogenic","Phelan-McDermid syndrome (22q13 deletion including SHANK3)","Autism (ADI-R and ADOS positive), language delay (first words 15 mo, first phrases 60 mo), very limited language, lost it at age 12 y, spontaneously; profound ID (Vineland at 21 y: Communication 19, Daily Living Skills 19, Socialization 19, Adaptive Behavior Composite 19). Full term birth, pyloric stenosis, surgery at 10 days old; no other major illness. Chronic encopresis. No dysmorphic features; hypotonia impacts ability to move arms and legs. Generalized seizures at age 16, abnormal EEG.","Both parents unaffected"]
["5240_4","M","Familial","European","Stage 1","Blood","Xp22.11","X:23116188-23280628",164441,"Loss","PTCHD1","Maternal (X-linked in a male)","qPCR, Illumina 1M-duo for sibs","present in 1 dizygotic twin brother with autism (5240_5) and 1 non-ASD sister (5240_3)","Pathogenic","PTCHD1 deletion of exon 1 and upstream region","Autism (based on ADI-R and ADOS), average non-verbal IQ (42%ile), low average language (18%ile), no epilepsy, sleep problems, no dysmorphic features. Deletion also present in dizygotic twin brother with autism (based on ADI-R and ADOS) and average IQ (reported in Marshall et al. 2008; Noor et al. 2010) ","Mother unaffected, some academic difficulties noted"]
["5126_4","M","Familial","European","Stage 1","CL","Xp21.3-p21.2","X:28931559-29478966",547408,"Gain","IL1RAPL1","Maternal (X-linked in a male)","qPCR, Agilent 1M","(1 brother with ASD, average IQ, epilepsy, abnormal brain MRI, no DNA) 4 unaffected sisters: CNV present in 2, absent in 1, no DNA for the other 2","Pathogenic","IL1RAPL1 intragenic duplication of exons 3-5; mutations and deletions cause XLID. This duplication is likely to disrupt the gene; additional studies are required to assess mRNA expression","Autism (based on ADI-R and ADOS), anxiety disorder, delayed language development, sat at 6 m and walked at 12 mo, low average IQ (5%ile), health history uneventful except for asthma as an infant. This subject also carries a DMD duplication of exon 1 of unknown clinical significance; when last evaluated at age 10 y, no obvious muscular difficulties were noted. ","Mother unaffected"]
["8597_201","M","Sporadic","European","Stage 2","Blood","Xp21.2-p21.1","X:31303978-32025062",721085,"Loss","DMD","Maternal (X-linked in a male)","qPCR","(not tested)","Pathogenic","DMD deletion of exons 45-60. DMD is involved in Duchenne/Becker muscular dystrophy; the deletion of exons 45-60 is predicted to lead to an in-frame deletion and a Becker phenotype, characterized by later onset and milder symptoms. There are at least 2 examples in the literature of similar deletions in Duchenne/Becker muscular dystrophy, in an affected male (no other information provided) (family D, Hung et al. 2005), and in a 5-generation family with a DMD phenotype (family 408; Taylor et al. 2007)","ASD diagnosis (autism on ADI-R and ASD on ADOS), no language delay, vision impairment (hypermetropia); average IQ (VIQ 97, PIQ 104, FSIQ 104); physical exam at 19 y: weight, height and head circumference 50%ile, no muscular deficit, no epilepsy, no information reported about muscular dystrophy/muscle problems in the family.","Mother ADHD, some degree of learning disability disorder and vision impairment; father vision impairment"]
["3019_3","M","Familial","European","Stage 1","Buccal","Xp21.1","X:32100618-32315937",215320,"Gain","DMD","Maternal (X-linked in a male)","qPCR","CNV present in affected brother, absent in healthy sister","Pathogenic","DMD duplication of exons 31-44, predicted to lead to an in-frame duplication and a Becker phenotype (sequencing coordinates: chrX:32097213-32321945, size: 224,733 bp)","Proband: autism (ADI-R and ADOS positive), language delay (first words 30 mo, first phrases 42 mo), normal IQ (WPPSI at 5 y 8 mo: VIQ 87, PIQ 76; British Picture Vocabulary Scale at 22 y 7 mo: VIQ 130), articulation dyspraxia, poor coordination, odd head movements and frequent body contortions.\nCNV also present in affected brother (3019-5): autism (ADI-R and ADOS positive), language delay (first words 12 mo, first phrases 60 mo), general developmental delay, mild ID (British Picture Vocabulary Scale at 11 y 2 mo: VIQ 62); as an adult has moderate learning difficulties. The medical notes do not mention any specific motor problems for either one of them. (Family reported in Pagnamenta et al. 2011a)","Both parents unaffected"]
["20013_1075001","M","Sporadic","European","Stage 2","CL","Xq28","X:153239048-153521797",282750,"Gain","ATP6AP1, CTAG1A, CTAG1B, DNASE1L1, EMD, FAM3A, FAM50A, FLNA, G6PD, GDI1, IKBKG, LAGE3, NCRNA00204, NCRNA00204B, PLXNA3, RPL10, SLC10A3, SNORA70, TAZ, UBL4A","De novo","qPCR, LR-PCR","(unaffected younger brother and sister, not tested)","Pathogenic","Xq28 duplication encompassing 20 genes, including 3 involved in ID: FLNA, GDI1, and IKBKG. Corresponds to the recurrent Xq28 duplication mediated by segmental duplications reported by Vandewalle et al. (2009) in families with XLID; GDI1 is the most likely candidate gene; its copy number correlates with the severity of clinical features (sequencing coordinates, chrX:153222048-153514311, size 292,264 bp) (see Highlighted genes in the Supplement)","Autism (ADI-R and ADOS positive), no language delay, normal IQ (WISC-III at 16 y: VIQ 93, PIQ 94, FSIQ 93), no dysmorphic features, head circumference –1.43 SD, normal neurological exam, no seizures","Father FSIQ 122, PIQ 116, VIQ 123, age at birth of child 24; evidence of social phobia (SADS), allergies, migraines; head circumference 58.3 cm, height 174.9 cm. Mother FSIQ 122, PIQ 125, VIQ 117, age at birth of child 22; asthma, symptoms of depression (SADS), head circumference 53.5 cm, height 158.4 cm"]
["14216_3470","M","Sporadic","European","Stage 1","Blood","Xq28","X:153263157-153474401",211245,"Gain","ATP6AP1, CTAG1A, CTAG1B, DNASE1L1, FAM3A, FAM50A, G6PD, GDI1, IKBKG, LAGE3, NCRNA00204, NCRNA00204B, PLXNA3, RPL10, SLC10A3, SNORA70, TAZ, UBL4A","Maternal (X-linked in a male)","qPCR","CNV present in 1 brother with developmental delay","Pathogenic","Xq28 duplication encompassing 18 genes, including 2 involved in ID: GDI1 and IKBKG. Recurrent Xq28 duplication implicated in XLID; GDI1 is the most likely candidate gene (see Highlighted genes in the Supplement)","Proband: autism (ADI-R and ADOS positive), neurodevelopmental delay with onset at 2 y (first words 18 mo, first phrases 48 mo), mild ID (VIQ 61, PIQ 65, FSIQ 72), no dysmorphic features, sleep problems, no epilepsy.\nBrother: confirmed learning disorder, may be mild intellectual disability (he is an adult now and was not evaluated formally for this study); also carries the CNV","Both parents unaffected"]
["Other pathogenic CNV (chromosomal abnormalities, large de novo CNV, small CNV (<30 kb), non stringent CNV or CNV identified with 1 algorithm only and validated)"]
["8658_201","F","Sporadic","European","Stage 2","Blood","1p21.3-p21.2","1:98175622-100923952",2748331,"Loss","AGL, CCDC76, CDC14A, DBT, FRRS1, GPR88, HIAT1, LOC100129620, LPPR4, LPPR5, LRRC39, MIR137, MIR553, PALMD, RTCD1, SASS6, SLC35A3, SNX7","De novo","qPCR","(2 healthy siblings, not tested)","Pathogenic","2.7 Mb 1p21.3-p21.2 deletion, de novo (18 genes, including DPYD and MIR137). 1p21.3 microdeletions comprising DPYD and MIR137 have been reported in 3 sibs and 2 unrelated cases with ID; the minimal region of overlap includes only these 2 genes (Willemsen et al. 2011). DPYD is involved in autosomal recessive dihydropyrimidine dehydrogenase deficiency. The cases displayed decreased miR-137 expression, suggesting the involvement of MIR137 in the 1p21.3 deletion phenotype (see Highlighted genes in the Supplement)","Autism on ADI-R and ADOS, comorbid ADHD, no language delay, low average IQ (WASI at 21 y: VIQ 78, PIQ 88, FSIQ 81); overweight, height and head circumference 50%ile, high pain tolerance, no epilepsy","Father healthy, mother hyperthyroidism"]
["5467_3","M","Sporadic","Other ","Stage 1","Blood","1q42.3-q44","1:233476547-247165725",13689179,"Gain","ACTN2, ADSS, AHCTF1, AKT3, ARID4B, B3GALNT2, C1orf100, C1orf101, C1orf150, C1orf229, CEP170, CHML, CHRM3, CNST, EDARADD, EFCAB2, ERO1LB, EXO1, FAM36A, FH, FMN2, GGPS1, GNG4, GPR137B, GREM2, HEATR1, HNRNPU, KIF26B, KMO, LGALS8, LOC100130331, LOC100287902, LOC148824, LOC149134, LOC339529, LOC339535, LOC646627, LOC731275, LYST, MAP1LC3C, MIR1537, MIR3123, MIR3124, MIR3916, MTR, NCRNA00201, NID1, NLRP3, OPN3, OR11L1, OR13G1, OR14A16, OR14C36, OR14I1, OR1C1, OR2AK2, OR2B11, OR2C3, OR2G2, OR2G3, OR2G6, OR2L13, OR2L1P, OR2L2, OR2L3, OR2L8, OR2M1P, OR2M2, OR2M3, OR2M4, OR2M5, OR2M7, OR2T1, OR2T10, OR2T11, OR2T12, OR2T2, OR2T27, OR2T29, OR2T3, OR2T33, OR2T34, OR2T35, OR2T4, OR2T5, OR2T6, OR2T8, OR2W3, OR2W5, OR6F1, PLD5, PPPDE1, RGS7, RPS7P5, RYR2, SCCPDH, SDCCAG8, SH3BP5L, SMYD3, TBCE, TFB2M, TRIM58, VN1R5, WDR64, ZNF124, ZNF238, ZNF496, ZNF669, ZNF670, ZNF670-ZNF695, ZNF672, ZNF692, ZNF695, ZP4","De novo","qPCR","(1 non-ASD brother, not tested)","Pathogenic","13.7 Mb 1q42.3-q44 duplication, de novo (114 genes). This CNV overlaps the critical region of the 1q43-q44 deletion syndrome. Distal duplications of the long arm of chromosome 1 are rare, reported in few cases in its pure form; 10 cases reported with trisomy 1q42-qter syndrome (chromosome abnormality)","Autism (based on ADI-R and ADOS), language delay, mild ID (WASI at 9 y 5 mo: VIQ 55, PIQ 62, FSIQ 56), no obvious dysmorphic features; no karyotype available","N/A"]
["5236_3","F","Familial","Other ","Stage 1","Blood","2p16.3","2:50705521-50719594",14074,"Loss","NRXN1","Maternal","Agilent 1M, qPCR","1 ASD brother, no CNV","Pathogenic","NRXN1 exonic deletion (CNV is exonic according to RefSeq, but not to UCSC) (<30 kb, non stringent: QSNP|PCNV)","Autism (based on ADI-R and ADOS), average non-verbal IQ (63%ile) based on Leiter-R, below average language (6%ile) based on OWLS. Possible pica but has not been confirmed as she does not ingest the items. If food is put in front of her she will keep eating until told to stop; if she does not have food presented to her she does not eat. Her mother reports that she cheats, lies, and cuts herself/her hair. It is also reported that \"something in her head tells her to do things\". No dysmorphic features, no other medical issues reported, no epilepsy","Mother: history of depression, especially post-partum depression following the birth of her son. Strong history of ASD on mother's side. Father: some difficulties with attention"]
["5328_3","M","Sporadic","Other ","Stage 1","CL","2p16.3","2:51044181-51120644",76464,"Loss","NRXN1","Paternal","Agilent 1M, qPCR","1 non-ASD sister, CNV; 1 non-ASD brother, no CNV","Pathogenic","NRXN1 exonic deletion (non stringent: QSNP|PCNV)","Autism (based on ADI-R and ADOS), below average non-verbal IQ (4%ile) based on Leiter at 5 y, language delay, at age 7 was moderately delayed in gross motor skills, no dysmorphic features except for a transverse palmar crease on the right hand, no epilepsy, normal EEG and head CT","Aboriginal descent, no parent phenotype data. Maternal family history of diabetes, rheumatoid arthritis, allergies, ASD and multiple sclerosis"]
["16037_1571015001","M","Sporadic","European","Stage 2","CL","2q37.3","2:239765200-239777909",12710,"Loss","HDAC4","Maternal","qPCR, LR-PCR","(healthy maternal half-brother, not tested)","Pathogenic","HDAC4 small intragenic deletion removing exon 4. Gene identified in 2010, responsible for some of the features of the 2q37 deletion syndrome (brachydactyly mental retardation syndrome). There are many 2q37 deletions reported in cases with ASD, but no mutations or single gene deletions of HDAC4 had been reported in ASD. (sequencing coordinates: chr2:239766528-239778481, size 11,954 bp) (<30 kb) (see Highlighted genes in the Supplement)","Autism (ADI-R and ADOS positive), language delay (first words and phrases 42 mo), verbal, borderline IQ (WISC-III at 21 y: VIQ 72, PIQ 87, FSIQ 77). Born at 37 weeks gestation, no congenital malformations, normal general exam. Had seizures at age 4-5, treated with depakote; treatment stopped for 2-3 years without seizure activity","Father schizophrenia, mother depression"]
["21020_1","M","Sporadic","European","Stage 2","CL (array), Blood (qPCR and FISH)","4p16.3-p16.1","4:53403-9016339",8962937,"Gain","ABCA11P, ABLIM2, ACOX3, ADD1, ADRA2C, AFAP1, AFAP1-AS1, ATP5I, C4orf10, C4orf42, C4orf44, C4orf48, C4orf6, CCDC96, CNO, CPLX1, CPZ, CRIPAK, CRMP1, CTBP1, CYTL1, D4S234E, DGKQ, DOK7, EVC, EVC2, FAM193A, FAM53A, FGFR3, FGFRL1, FLJ36777, GAK, GPR78, GRK4, GRPEL1, HAUS3, HGFAC, HTRA3, HTT, IDUA, JAKMIP1, KIAA0232, KIAA1530, LETM1, LOC100129917, LOC100129931, LOC100130872, LOC100133461, LOC100507266, LOC285484, LOC348926, LOC402160, LOC728373, LOC728379, LOC728393, LOC728400, LOC728405, LOC93622, LRPAP1, LYAR, MAEA, MAN2B2, METTL19, MFSD10, MFSD7, MIR4274, MIR943, MRFAP1, MRFAP1L1, MSX1, MXD4, MYL5, NAT8L, NOP14, OTOP1, PCGF3, PDE6B, PIGG, POLN, PPP2R2C, PSAPL1, RGS12, RNF212, RNF4, S100P, SCARNA22, SH3BP2, SH3TC1, SLBP, SLC26A1, SORCS2, SPON2, STK32B, STX18, TACC3, TADA2B, TBC1D14, TMED11P, TMEM128, TMEM129, TMEM175, TNIP2, USP17, USP17L5, USP17L6P, WFS1, WHSC1, WHSC2, ZBTB49, ZFYVE28, ZNF141, ZNF595, ZNF718, ZNF721, ZNF732, ZNF876P","De novo","qPCR, FISH","(not tested)","Pathogenic","De novo unbalanced translocation leading to 4p16.3p16.1 duplication and 8p23.3p23.1 deletion. The 4p terminal duplication spans 8.9 Mb and involves the region implicated in Wolf-Hirschhorn syndrome. Normal 46,XY karyotype, unbalanced translocation shown by FISH, 46,XY, der(8)t(4;8)(4p16.1→ter;8p23.1→ter). (chromosome abnormality)","Autism, language delay, verbal, moderate ID, prominent comorbid OCD, overgrowth. Physical exam at 21 y: macrocephalic (head circumference 60 cm, 1.5 cm greater than the 98%ile), weight 102.5 kg (1.5 kg greater than the 97%ile), height 183 cm (75-90%ile); scaphocephalic, extra fold in the cartilage at the superior aspect of each pinna, prominent lower lip, left upper canine tooth congenitally absent, duplicate set of wisdom teeth in his lower jaw, scoliosis, mild generalized hypotonia, no history of epilepsy","Both parents healthy"]
["21020_1","M","Sporadic","European","Stage 2","CL (array), Blood (qPCR and FISH)","8p23.3-p23.1","8:154984-6994825",6839842,"Loss","AGPAT5, ANGPT2, ARHGEF10, C8orf42, CLN8, CSMD1, DEFA1, DEFA10P, DEFA1B, DEFA3, DEFA4, DEFA5, DEFA6, DEFB1, DEFT1P, DEFT1P2, DLGAP2, ERICH1, FBXO25, KBTBD11, LOC286083, MCPH1, MIR596, MYOM2, RPL23AP53, XKR5, ZNF596","De novo","qPCR, FISH","(not tested)","Pathogenic","De novo unbalanced translocation leading to 4p16.3p16.1 duplication and 8p23.3p23.1 deletion (see above). The 8p terminal deletion spans 6.8 Mb; numerous terminal deletions of 8p have been described in the literature; common features include mild dysmorphic features, ear abnormalities, widely spaced nipples, subtle skull shape abnormalities, microcephaly, growth retardation, behavior issues and developmental and speech delay (Burnside et al. 2013). The deletion encompasses DLGAP2, encoding a post-synaptic density protein. (chromosome abnormality)","(see above)","Both parents healthy"]
["14270_3930","F","Sporadic","European","Stage 1","Blood","6q25.3-q27","6:160773919-170761395",9987477,"Gain","AGPAT4, BRP44L, C6orf118, C6orf120, C6orf123, C6orf124, C6orf176, C6orf208, C6orf70, CCR6, DACT2, DKFZp451B082, DLL1, FAM120B, FGFR1OP, FRMD1, GPR31, HGC6.3, KIF25, LOC100526820, LOC154449, LOC285796, LOC441177, LPA, LPAL2, MAP3K4, MIR1913, MIR3939, MLLT4, NCRNA00241, NCRNA00242, PACRG, PARK2, PDCD2, PDE10A, PHF10, PLG, PRR18, PSMB1, QKI, RNASET2, RPS6KA2, SFT2D1, SLC22A3, SMOC2, T, TBP, TCP10, TCP10L2, TCTE3, THBS2, TTLL2, UNC93A, WDR27","De novo","FISH","(1 healthy sibling, not tested)","Pathogenic","10 Mb duplication 6q25.3-q27, de novo, identified with the SNP array. High resolution karyotype was normal; subtelomere FISH analysis revealed a 6q terminal duplication arising from a paternal balanced translocation, 46,XY, t(6;22)(q25.3;p11.2). The father is healthy. The case's karyotype is: 46,XX.ish der(22)t(6;22)(6q25.3;p11.2)pat(6qtel+). \"6q duplication syndrome\" is a rare cytogenetic abnormality reported in few cases in its pure form; the duplications can affect any part of the 6q arm and few overlap. Most of the reported cases are the result of abnormal segregation of a balanced translocation carried by a parent, like in this case. (chromosome abnormality)","Autism (ADI-R and ADOS positive), mild ID (VIQ 50, PIQ 57, FSIQ 56), speech delay (first words 30 mo, first phrases 72 mo), myopia and astigmatism, no dysmorphic features, no epilepsy","Both parents unaffected"]
["8404_201","M","Familial (paternal cousin high functioning ASD)","European","Stage 2","Blood","6q27","6:169136788-170761395",1624608,"Loss","C6orf120, C6orf208, C6orf70, DLL1, FAM120B, LOC154449, NCRNA00242, PDCD2, PHF10, PSMB1, TBP, TCTE3, THBS2, WDR27","De novo","qPCR","(2 healhy sisters, not tested)","Pathogenic","1.6 Mb de novo deletion in 6q27 region (14 genes). Terminal 6q deletion syndrome. The CNV contains DLL1, an ASD candidate gene (de novo frameshift variant identified in ASD exome study, Iossifov et al. 2012)","Autism, low average IQ (WISC-III at 15 y: VIQ 84, PIQ 84, FSIQ 83)","N/A"]
["13137_1543","F","Sporadic","European","Stage 1","Blood","8p12-8q12.1 ","8:31928590-58996070",27067481,"Gain","ADAM18, ADAM2, ADAM32, ADAM3A, ADAM5P, ADAM9, ADRB3, AGPAT6, ANK1, AP3M2, ASH2L, ATP6V1H, BAG4, BRF2, C8orf22, C8orf4, C8orf40, C8orf41, C8orf71, C8orf86, CEBPD, CHCHD7, CHRNA6, CHRNB3, DDHD2, DKK4, DUSP26, EFCAB1, EIF4EBP1, ERLIN2, FAM150A, FGFR1, FNTA, FUT10, GINS4, GOLGA7, GOT1L1, GPR124, HGSNAT, HOOK3, HTRA4, IDO1, IDO2, IKBKB, IMPAD1, KCNU1, KIAA0146, LETM2, LOC100287846, LOC100507632, LOC100507651, LOC728024, LSM1, LYN, LYPLA1, MAK16, MCM4, MIR486, MOS, MRPL15, MYST3, NCRNA00293, NKX6-3, NPBWR1, NRG1, OPRK1, PCMTD1, PENK, PLAG1, PLAT, PLEKHA2, POLB, POTEA, PPAPDC1B, PRKDC, PROSC, PXDNL, RAB11FIP1, RB1CC1, RGS20, RNF122, RNF170, RNF5P1, RP1, RPS20, SBF1P1, SDR16C5, SFRP1, SGK196, SLC20A2, SNAI2, SNORD54, SNTG1, SOX17, ST18, STAR, TACC1, TCEA1, TGS1, THAP1, TM2D2, TMEM68, UBE2V2, UNC5D, VDAC3, WHSC1L1, XKR4, ZMAT4, ZNF703","De novo","karyotype","(no siblings)","Pathogenic","27 Mb pericentromeric duplication 8p12-8q12.1, de novo. The karyotype revealed a mosaic supernumerary ring chromosome (47, XX, +r[10]/46, XX[70]) of unknown origin, shown to involve chromosome 8 by the SNP array. Trisomy 8 syndrome is characterized by mild to severe mental and growth deficiency, facial dysmorphisms, and limb abnormalities. Other features include urinary tract, cardiac and skeletal defects. In cases of supernumerary marker chromosomes or supernumerary ring chromosomes derived from chromosome 8, mosaic or non-mosaic, the clinical presentation varies from normal phenotype to features overlapping the trisomy 8 syndrome (chromosome abnormality)","This case was excluded from AGP after the chromosomal abnormality was identified; no phenotype information available","N/A"]
["8534_201","M","Sporadic","European","Stage 2","Blood","10q11.21-q11.23","10:45633089-51564756",5931668,"Loss","AGAP4, AGAP6, AGAP7, AGAP8, AGAP9, ANTXRL, ANXA8, ANXA8L1, ANXA8L2, ARHGAP22, BMS1P1, BMS1P5, C10orf128, C10orf53, C10orf71, C10orf72, CHAT, CTSL1P2, DRGX, ERCC6, FAM170B, FAM21A, FAM21B, FAM25B, FAM25C, FAM25G, FAM35B, FAM35B2, FLJ31813, FRMPD2, FRMPD2P1, GDF10, GDF2, GPRIN2, LOC399753, LOC642826, LOC643650, LOC728407, LOC728643, LRRC18, MAPK8, MIR4294, MSMB, NCOA4, OGDHL, PARG, PGBD3, PPYR1, PTPN20A, PTPN20B, RBP3, SLC18A3, SYT15, TIMM23, WDFY4, ZNF488","De novo","qPCR","(1 healthy brother and 1 healthy sister, not tested)","Pathogenic","5.9 Mb de novo deletion in 10q11.21-q11.23 region (56 genes). Recurrent deletions and reciprocal duplications have been reported in this region (Stankiewicz et al. 2012). Sizes vary, but most breakpoints fall in segmental duplications. The phenotype associated with the deletion includes variable clinical features, with developmental delay and/or ID as the only features common to the majority of individuals. While no deletions were identified in controls, the frequency of the duplications was not different between cases and controls. Most deletions are inherited from apparently normal parents, indicating variable expressivity/incomplete penetrance. All deletions overlap a 1.5 Mb region between 49.2 and 50.6 Mb, encompassing 11 genes, where complete deletions have not been reported in control populations. CHAT (choline acetyltransferase) and SLC18A3 (vesicular acetylcholine transporter) may contribute to some of the features present in individuals with the deletion.","Autism on ADI, ASD on ADOS; VIQ 136, PIQ 105; physical exam at 23 y: overweight (+3.6 SD, BMI 30.4), normal height, head circumference +2 SD, Duane syndrome (congenital disorder of eye movement), no epilepsy","Mother congenital hearing loss, peculiar gait, shyness in childhood, rigidity, eating disorder; father unaffected"]
["4312_1","M","Sporadic","European","Stage 2","Blood","10q11.21-q11.23","10:45550419-51496386",5945968,"Loss","AGAP4, AGAP6, AGAP7, AGAP8, AGAP9, ANTXRL, ANXA8, ANXA8L1, ANXA8L2, ARHGAP22, BMS1P1, BMS1P5, C10orf128, C10orf53, C10orf71, C10orf72, CHAT, CTSL1P2, DRGX, ERCC6, FAM170B, FAM21B, FAM21C, FAM25B, FAM25C, FAM25G, FAM35B, FAM35B2, FLJ31813, FRMPD2, FRMPD2P1, GDF10, GDF2, GPRIN2, LOC399753, LOC642826, LOC643650, LOC728407, LOC728643, LRRC18, MAPK8, MIR4294, MSMB, NCOA4, OGDHL, PARG, PGBD3, PPYR1, PTPN20A, PTPN20B, RBP3, SLC18A3, SYT15, TIMM23, WDFY4, ZNF488","Paternal","qPCR","CNV present in 1 unaffected sister (normocephalic, no health issues), absent in 1 non-ASD brother with ADHD and bipolar disorder","Pathogenic","5.9 Mb paternal deletion in 10q11.21-q11.23 region (56 genes). Recurrent deletions have been reported in this region, associated with variable expressivity/incomplete penetrance (see above)","Autism (based on ADI-R and ADOS), language regression at 20 mo, first phrases at 96 mo, mild ID (Leiter PIQ 54), ADHD features, asthma, allergies, macrocephaly, birthmark at base of neck, small spot in mid back thought to be a meningomyelocele; no epilepsy; birth complications, hypotonic at birth (reported in Griswold et al. 2012a; family 17500)","Father kidney stones, normocephalic, no other features; mother history of depression and anxiety/panic disorder, hypothyroid"]
["6053_3","M","Familial","European","Stage 1","Unknown (blood or CL)","12q13.3-q14.1","12:54218922-58779615",4560694,"Gain","AGAP2, ANKRD52, APOF, ARHGAP9, ARHGEF25, ATP5B, AVIL, B4GALNT1, BAZ2A, BLOC1S1, BLOC1S1-RDH5, CD63, CDK2, CDK4, CNPY2, COQ10A, CS, CTDSP2, CYP27B1, DCTN2, DDIT3, DGKA, DNAJC14, DTX3, ERBB3, ESYT1, GDF11, GLI1, GLS2, GPR182, HSD17B6, IKZF4, IL23A, INHBC, INHBE, ITGA7, KIF5A, LOC100130776, LOC100506844, LOC440104, LRIG3, LRP1, MARCH9, MARS, MBD6, METTL1, METTL21B, METTL7B, MIP, MIR1228, MIR26A2, MMP19, MYL6, MYL6B, MYO1A, NAB2, NACA, NDUFA4L2, NXPH4, OBFC2B, OR10P1, OR6C4, ORMDL2, OS9, PA2G4, PAN2, PIP4K2C, PMEL, PRIM1, PTGES3, R3HDM2, RAB5B, RBMS2, RDH16, RDH5, RNF41, RPL41, RPS26, SARNP, SDR9C7, SHMT2, SLC16A7, SLC26A10, SLC39A5, SMARCC2, SNORD59A, SNORD59B, SPRYD4, STAC3, STAT2, STAT6, SUOX, TAC3, TIMELESS, TMEM194A, TSFM, TSPAN31, WIBG, XRCC6BP1, ZBTB39, ZC3H10","De novo","qPCR","CNV absent in 1 sister with Asperger syndrome","Pathogenic","4.5 Mb de novo duplication in 12q13 (101 genes). No similar CNV reported; a 12q13.3q14.1 duplication (51.6-56.5 Mb) overlapping 2 Mb was reported in a girl with a Wolf-Hirschhorn syndrome phenotype (Dallapiccola et al. 2009)","Autism, moderate ID, language delay, normal physical exam","Mother bipolar disorder, father healthy"]
["14070_1230","M","Familial","European","Stage 1","Blood","15q26.1","15:91200007-91283004",82998,"Loss","CHD2, LOC100507217, MIR3175","De novo","qPCR","(1 brother with ASD not tested)","Pathogenic","CHD2 exonic deletion. CHD2 de novo mutations reported recently in epileptic encephalopathy and ID; several deletions reported in cases with ID, ASD and epilepsy (see Highlighted genes in the Supplement)","Proband (14070-1230), 14 yo: autism (meets criteria on ADI-R and ADOS), walked at 14 mo, first words 24 mo, phrases 26 mo, currently verbal, ID (Griffiths: language DQ 68, performance DQ 46, global DQ 53); normal growth, normal neurological exam; minor dysmorphic features: micrognatia, protruding ears; no epilepsy; brain MRI: altered angular gyrus (normal variant, unknown pathological significance). \nHis 12 yo brother harbors the same deletion; he has mild autism according to ADOS, walked at 15 mo, first words 24 mo, phrases 36 mo, verbal, ID (Griffiths: language DQ 65, performance DQ 61, global DQ 51); normal growth, normal neurological exam; minor dysmorphic features similar to his brother (micrognatia, protruding ears); epilepsy, onset 9 y, partial with secondary generalization, difficult to control with carbamazepine; EEG showed paroxistic activity in left temporal lobe","Both parents healthy"]
["5420_3","M","Sporadic","European","Stage 1","CL","whole chr 21","21:1-247249719",247249719,"Gain","whole chromosome 21","De novo","karyotype","(1 non-ASD brother, not tested)","Pathogenic","Down syndrome (47,XY+21) (chromosome abnormality)","Autism (based on ADI, ADOS and DSM-IV criteria), speech language impairment, self-stimulatory behaviors including mouthing and licking objects, finger flicking, pacing, fascination with fans and picture frames, delayed milestones (walked independently at age 7, first single words age 6, 2-3 word phrases age 9 but with a vocabulary of hundreds of words and verbally requesting). Has typical stigmata of Down syndrome, tall forehead with brachycephaly, small hypopigmented patch in the glabellar area and one small irregular café-au-lait spot near his frontal hairline, upslanting palpebral fissures with bilateral epicanthal folds, blue irides with Brushfield spots, wide downturned mouth, lowset ears, small hands with brachydactyly, normal palmar creases, no clinodactyly of the fingers. Hypotonic throughout, normal deep tendon reflexes, unusually wide-based gait; no epilepsy","N/A"]
["14291_4120","F","Sporadic","European","Stage 2","CL","22q13.33","22:49470371-49480446",10076,"Loss","SHANK3","De novo","LR-PCR","(no siblings)","Pathogenic","SHANK3 exonic deletion (exons 9-13) (<30 kb, called with 1 algorithm only: PCNV) (sequencing coordinates: 49468716-49485255, size 16,540 bp)","Autism on ADI-R, ASD on ADOS, language delay (first words 9 mo, first phrases 40 mo), walked at 10 mo, verbal (speaks fluently, spontaneously, with clear pronunciation, but with limited language and without complex sentences), no ID (Griffiths at 5 y: language DQ 69, performance DQ 109, global DQ 93), no dysmorphic features or other anomalies, normal neurological exam, normal growth, no epilepsy. Negative family history.","Both parents unaffected"]
["5241_3","M","Familial","European","Stage 1","Blood","Xp21.1","X:31793278-31822704",29427,"Loss","DMD","Maternal (X-linked in a male)","qPCR","1 brother with ASD, no CNV","Pathogenic","DMD deletion of exon 48 (predicted to lead to an in-frame deletion) (<30 kb)","Autism (based on ADI-R and ADOS), no language delay, low non-verbal IQ (9%ile), average language (47%ile), no epilepsy, right 2-3 toe syndactyly, right ear malformation","Mother anxiety disorder, OCD, history of seizures, mild attention difficulties"]
["9861_202","M","Sporadic","Other ","Stage 2","Blood","Xp11.4","X:41248675-41259467",10793,"Gain","CASK","Maternal (X-linked in a male)","qPCR","(not tested)","Pathogenic","CASK partial duplication of the 5' UTR of exon 1 in a male, maternal. CASK mRNA expression in peripheral blood lymphocytes from the proband was decreased. CASK loss-of-function mutations and deletions cause severe ID with microcephaly, brain malformations, congenital nystagmus and dysmorphic facial features in females. Only a few cases have been reported in males, in which loss-of-function CASK mutations cause early-onset epileptic encephalopathy and pontocerebellar hypoplasia. In contrast, missense or hypomorphic mutations result in mild ID with or without nystagmus, mostly in males (<30 kb, called with 1 algorithm only: PCNV)","Autism (autism on ADI-R, ASD on ADOS), delayed speech (first words 36 mo, first phrases 72 mo), limited language at 7 y; average IQ (Leiter-R at 7 y: VIQ 90); epilepsy started at 6 y, treated. No dysmorphic features, normal physical exam; normal height, weight and head circumference. Brain CT scan: frontal cortical atrophy; normal audiometry","Both parents healthy"]
["5257_3","M","Sporadic","European","Stage 1","Blood","Yp11.32-q12","Y:1-57772954",57772954,"Gain","Entire chromosome Y","De novo","karyotype","(unaffected brother not tested)","Pathogenic","XYY syndrome. 1 in 1000 boys has a 47,XYY karyotype. The majority are never diagnosed; most are diagnosed because of developmental delays, behavioral problems such as ASD and ADHD, and tall stature. Individuals with XYY are at increased risk for ASD, with a diagnosis of ASD found in 19% (11/58) and 29% (26/90) males with XYY in 2 recent studies (Bishop et al. 2011; Bardsley et al.2013) (chromosome abnormality)","Autism (based on ADI-R and ADOS), language delay (first words 57 mo), no functional language, mild ID (Leiter PIQ 58), no epilepsy, no dysmorphic features","Mother meets criteria for broad autism phenotype (based on Pragmatic Rating Scale self report); father sleep apnea"]
["5515_3","M","Sporadic","European","Stage 1","Blood","Yp11.32-q12","Y:1-57772954",57772954,"Gain","Entire chromosome Y","De novo","karyotype","(unaffected sister not tested)","Pathogenic","XYY syndrome (see above) (chromosome abnormality)","Autism (based on ADI-R and ADOS), language delay (first words 36 mo, first phrases 39 mo), verbal, high average IQ (WAIS-III: VIQ 111, PIQ 121, FSIQ 117), height and weight high average, strabismus, sleep apnea, reported high pain tolerance; mild dysmorphic features: deep set eyes, narrow palpebral fissures (familial), hooded eyelids, tall forehead, widow’s peak, and prominent central incisors; no epilepsy","Neither parent meets broad autism phenotype cutoffs (based on Pragmatic Rating Scale); mother thyroid issues, sleep apnea"]
[]
["Variants of uncertain clinical significance (this list is not exhaustive, it includes CNV overlapping ASD/ID genes/loci, plus chromosomal abnormalities and large de novo or inherited CNV of unknown clinical significance)"]
["CNV overlapping ASD/ID genes or loci (stringent, > 30 kb)"]
["6356_5","M","Sporadic","European","Stage 1","Blood","1p36.33p36.32","1:2118508-2325536",207029,"Loss","C1orf86, LOC100129534, MORN1, RER1, SKI","De novo","qPCR","(2 healthy sibs, no DNA)","Uncertain","Rare de novo deletion encompassing 5 genes, including SKI; SKI is involved in Shprintzen-Goldberg syndrome through dominant negative mutations","Autism, no language delay, moderate ID, normal physical exam, no epilepsy","Both parents unaffected"]
["6317_5","M","Sporadic","European","Stage 1","Blood","1p36.11","1:26767083-26941756",174674,"Gain","ARID1A, RPS6KA1","Paternal","qPCR","(2 sibs, no DNA)","Uncertain","Partial duplication of 2 genes, including ARID1A; ARID1A mutations reported recently in Coffin-Siris syndrome","Autism, language delay, functional language, dysarthria, mild ID, chronic otitis media, bilateral hypermetropia and astigmatism, macrocephaly (+2 SD), weight +3 SD, height +1 SD, no dysmorphic features, hypotonia, no epilepsy, normal brain MRI","Both parents reportedly healthy"]
["13027_353","F","Unknown","European","Stage 1","Blood","2q22.3","2:144837809-145315383",477575,"Gain","DKFZp686O1327, ZEB2","De novo","qPCR","(not tested)","Uncertain","Duplication of 2 genes, including ZEB2, de novo; mutations and deletions in ZEB2 cause Mowat-Wilson syndrome","Autism on ADI-R and ADOS, verbal, moderate ID","No information"]
["3424_3","M","Sporadic","European","Stage 1","Blood","2q23.1","2:148881443-149078468",197026,"Gain","MBD5","Maternal","qPCR","absent in 1 unaffected brother","Uncertain","MBD5 partial duplication; MBD5 is implicated in autosomal dominant ID through deletions (2q23.1 deletion syndrome) and mutations","Autism, mild ID, relative macrocephaly, no dysmorphic features","Mother unaffected"]
["3599_3","F","Sporadic","European","Stage 2","Blood","6q25.3","6:155906594-157336808",1430215,"Gain","ARID1B","Paternal","qPCR","CNV also present in unaffected sister","Uncertain-likely benign","ARID1B partial duplication; haploinsufficiency of ARID1B causes ID and Coffin-Siris syndrome. CNV also present in healthy father and sister; proband has normal ARID1B mRNA expression in blood; unlikely to be pathogenic","Autism (based on ADI-R and ADOS), normal physical growth in first years, delayed early language development (first words 24 mo, first phrases 36 mo) and delay in motor development. Currently verbal, below average verbal IQ (PPVT 84), average non-verbal IQ (Raven 98). No growth abnormalities, overweight, coarse facial features, bulbous nose tip, mild hypertrichosis in the face, abnormally formed ears, normal fingernails; no epilepsy","Father healthy; thin upper lip, coarse facial features (less pronounced), mild bulbous nasal tip; mother healthy, no facial dysmorphic features"]
["13037_463","M","Sporadic","European","Stage 1","Blood","9q34.3","9:137682721-137840339",157619,"Loss","CAMSAP1, KCNT1, LCN9, SOHLH1","Maternal","no validation attempted","(not tested)","Uncertain","Deletion encompassing 4 genes, including the potassium channel KCNT1; gain-of-function KCNT1 mutations cause malignant migrating partial seizures of infancy","Autism, severe speech and language delay, mild ID, no dysmorphic features. This case also has a de novo NRXN1 exonic deletion.","No information"]
["16072_1571036001","M","Sporadic","European","Stage 2","CL","11p15.5","11:381049-1019320",638272,"Gain","ANO9, AP2A2, C11orf35, CD151, CDHR5, CEND1, CHID1, DEAF1, DRD4, EFCAB4A, EPS8L2, HRAS, IRF7, LOC143666, LRRC56, MIR210, MIR210HG, MUC6, PDDC1, PHRF1, PIDD, PKP3, PNPLA2, POLR2L, PTDSS2, RASSF7, RNH1, RPLP2, SCT, SIGIRR, SLC25A22, SNORA52, TALDO1, TMEM80, TSPAN4","Paternal","qPCR","(unaffected sibling not tested)","Uncertain","638 kb duplication encompassing 35 genes, including HRAS (involved in Costello syndrome through activating mutations); although duplication of HRAS is not expected to be pathogenic, the contribution of other genes in the interval is unknown","Autism (autism on ADI-R and ADOS), language delay (first words 42 mo, first phrases 48 mo), verbal, below average IQ (WISC-III at 30 y: VIQ 73, PIQ 87, FSIQ 78); possible lead poisoning at age 2 from house paint (family moved afterwards); no seizures","Both parents unaffected"]
["20070_1331001","M","Sporadic","European","Stage 2","Blood","16p13.11","16:14808871-15935225",1126355,"Gain","ABCC6P2, C16orf45, FOPNL, KIAA0430, MIR1972-1, MIR1972-2, MIR3179-1, MIR3179-2, MIR3179-3, MIR3180-1, MIR3180-2, MIR3180-3, MIR3180-4, MIR484, MPV17L, MYH11, NDE1, NOMO1, NPIP, NTAN1, PDXDC1, RRN3","Maternal","qPCR","(not tested)","Uncertain","16p13.11 microduplication. Recurrent 16p13.11 deletions are associated with variable phenotype and incomplete penetrance, and have been reported in subjects with diverse neuropsychiatric disorders, including ID, ASD, schizophrenia and epilepsy, sometimes inherited from unaffected parents. Duplications have been described in neurodevelopmental disorders and in controls, with studies reporting either no enrichment or a small but significant enrichment in cases. Further studies in larger case populations and controls are needed to clarify their role as risk factors","Autism on ADI-R and ADOS, no language delay, normal IQ (Differential Abilities Scale at 8 y 6 mo: VIQ 118, PIQ 95, FSIQ 104), self-injurious behavior, normal head circumference","Mother: adult SRS total 31, normal head circumference"]
["9766_202","M","Sporadic","Other ","Stage 2","Blood","16p13.11","16:15032942-16199484",1166543,"Gain","ABCC1, ABCC6, C16orf45, FOPNL, KIAA0430, MIR3180-4, MIR484, MPV17L, MYH11, NDE1, NTAN1, PDXDC1, RRN3","Maternal","qPCR","(no siblings)","Uncertain","16p13.11 microduplication (see above)","Autism (autism on ADI-R and ADOS), no language delay, functional language, no ID (WISC-R at age 8 y: VIQ 105, PIQ 85, FSIQ 94), normal height and weight, head circumference -2.5 SD, no dysmorphic features, normal physical exam, no epilepsy","Mother migraine, father asthma, otherwise both are healthy. Paternal first degree cousin possible Asperger, mother's uncle possible schizophrenia"]
["4182_1","M","Sporadic","European","Stage 2","Blood","16p13.11","16:15387380-16199484",812105,"Gain","ABCC1, ABCC6, C16orf45, FOPNL, KIAA0430, MIR484, MPV17L, MYH11, NDE1","Maternal","no validation attempted","(not tested)","Uncertain","16p13.11 microduplication (see above)","Autism (based on medical history and ADI-R), verbal with history of language regression and delay, borderline ID (Vineland Adaptive Behavior Composite score 70 at 2 y), no dysmorphic features, asthma. Identical twin also has ASD","Mother hypothyroidism, vision loss, possible multiple sclerosis, trisomy X (retroverted uterus, menopause at age 43); father features of ASD, irritability and aggression"]
["14142_2400","M","Sporadic","European","Stage 1","Blood","16p13.11 ","16:15387380-16256106",868727,"Gain","ABCC1, ABCC6, C16orf45, FOPNL, KIAA0430, MIR484, MPV17L, MYH11, NDE1, NOMO3","Paternal","qPCR","(no siblings)","Uncertain","16p13.11 microduplication (see above)","Autism (ADI-R and ADOS positive), speech delay (first words 36 mo, first phrases 60 mo), mild ID (WISC: VIQ 60, PIQ 61, FSIQ 57), no dysmorphic features, no epilepsy","Both parents unaffected"]
["5258_3","M","Sporadic","European","Stage 1","Blood","16p13.11 ","16:15387380-16270740",883361,"Gain","ABCC1, ABCC6, C16orf45, FOPNL, KIAA0430, MIR484, MPV17L, MYH11, NDE1, NOMO3","Paternal","qPCR, Illumina 1M-duo for sib","1 non-ASD paternal half-sister, no CNV","Uncertain","16p13.11 microduplication (see above)","Autism (based on ADI-R and ADOS), language delay, average IQ, history of torticollis and hydrocele, no epilepsy, normal brain CT","Father unaffected"]
["2265_1","M","Sporadic","European","Stage 2","Blood","16p12.3,16p13.11","16:15387380-18176669",2789290,"Gain","ABCC1, ABCC6, C16orf45, FOPNL, KIAA0430, MIR3179-1, MIR3179-2, MIR3179-3, MIR3180-1, MIR3180-2, MIR3180-3, MIR484, MPV17L, MYH11, NDE1, NOMO3, PKD1P1, XYLT1","Maternal","qPCR","(3 unaffected half-siblings, 1 maternal and 2 paternal, no DNA)","Uncertain","16p13.11 microduplication (see above)","Autism (meets ADI-R and ADOS criteria), language delay, limited language (does not use 3 word phrases), developmental delay (WASI at 18 y: VIQ 55, PIQ 86, FSIQ 70), OCD, self-injurious behavior, obesity (BMI 37), macrocephaly (>3 SD), normal height (1.1 SD), slopping forehead, short hands, tapering fingers, sandal gap on right foot, no epilepsy, normal brain CT scan. History of gastroesophageal reflux disease, gastritis, depression, and Guillain-Barré syndrome","Mother anxiety/panic disorder, depression; father unaffected"]
["8703_201","M","Sporadic","European","Stage 2","Blood","17p13.3","17:1092256-1249222",156967,"Gain","BHLHA9, TUSC5, YWHAE","Paternal","qPCR","no CNV in unaffected sib","Uncertain-likely benign","Duplication encompassing 3 genes, partially overlapping YWHAE; whole duplications are pathogenic (17p13.3 duplication syndrome); there is an AGP control with a YWHAE partial duplication; several partial duplications reported in DGV","Autism (ADI-R and ADOS positive), OCD and depression; gross and fine motor delays; speech delay (first words 30 mo, first phrases 36 mo), odd intonation and loud volume; normal IQ (WASI at 17 y: VIQ 104, PIQ 118, FSIQ 111); stiff and unusual gait, toe-walking; dyspraxia; overgrowth, long narrow head; no seizures, normal brain MRI","Father diagnosed with depression and ADHD; no diagnosis of OCD but mild symptoms; shows broader autism phenotypic characteristics including social abnormalities during childhood and currently (few friendships, shyness, aloofness; circumscribed interests and reported rigid personality). Language delay and continued articulation errors. Neuropsychological testing revealed manual motor impairments."]
["5444_3","M","Sporadic","European","Stage 1","Blood","17q25.3","17:76953064-77782267",829204,"Gain","ACTG1, ANAPC11, ARHGDIA, ARL16, ASPSCR1, BAHCC1, C17orf70, C17orf90, CCDC137, CCDC57, DCXR, DUS1L, DYSFIP1, FASN, FSCN2, GPS1, HGS, LOC92659, LRRC45, MAFG, MIR3186, MRPL12, MYADML2, NOTUM, NPB, NPLOC4, P4HB, PCYT2, PDE6G, PYCR1, RAC3, RFNG, SIRT7, SLC16A3, SLC25A10, STRA13, THOC4, TSPAN10","De novo","qPCR","1 non-ASD sister, no CNV","Uncertain","829 kb duplication encompassing 38 genes, including ACTG1 (involved in Baraitser-Winter syndrome through dominant-negative or gain-of-function missense mutations); although duplication of ACTG1 is not expected to be pathogenic, the contribution of the other genes in the interval is unknown. Tandem duplication; distal breakpoint intersects SLC16A3","Autism (based on ADI-R and ADOS), ID (unable to complete IQ measure), below average language (1%ile), regression of language and motor skills at age 3 y, myoclonic epilepsy, self-injurious behavior, sleep disorder (altered circadian rhythm according to parents), no dysmorphic features","Both parents are very social"]
["14242_3660","F","Sporadic","European","Stage 1","Blood","22q11.23","22:21995356-22598120",602765,"Gain","C22orf15, C22orf43, CES5AP1, CHCHD10, DERL3, IGLL1, LOC91316, MIF, MMP11, RGL4, SLC2A11, SMARCB1, VPREB3, ZDHHC8P1, ZNF70","Maternal","no validation attempted","(no siblings)","Uncertain","602 kb duplication encompassing 15 genes, including SMARCB1; mutations reported recently in Coffin-Siris syndrome","Autism (ADI-R and ADOS positive), neurodevelopmental delay with onset at 2 y (first words 24 mo, first phrases 42 mo), normal IQ (Griffiths at 4 y 1 mo: language DQ 110, performance DQ 98, global DQ 99), no dysmorphic features, no epilepsy","Both parents unaffected"]
["6381_3","M","Sporadic","European","Stage 2","Blood","Xp21.2","X:30521738-30789831",268094,"Gain","GK, TAB3","Maternal (X-linked in a male)","qPCR","(1 healthy brother, no DNA)","Uncertain","Duplication of 2 genes, partially overlapping GK; GK mutations and deletions cause XLID","Autism, language delay, limited language, severe ID, early-onset obesity (+4 SD), normal height, macrocephaly (+3 SD), big ears, shield-like chest, no other dysmorphic features, bilateral hypermetropia, epilepsy, normal brain MRI","Mother epilepsy, father unaffected"]
["5126_4","M","Familial","European","Stage 1","CL","Xp21.1","X:32948977-33330592",381616,"Gain","DMD","Maternal (X-linked in a male)","Agilent 1M","(1 brother with ASD, average IQ, epilepsy, abnormal brain MRI, no DNA) 4 unaffected sisters: CNV present in 2, absent in 1, no DNA for the other 2","Uncertain","DMD duplication of exon 1 of the Dp427 transcripts. The effect of this duplication is difficult to predict. According to the Leiden Muscular Dystrophy pages (http://www.dmd.nl), duplication including the transcription initiation and start site (first exon) may produce a normal transcript (initiated at the duplicated first exon), a transcript containing the duplicated exon or a combination of both. Experimental evidence at the RNA level is required to interpret the significance of this CNV.","Autism (based on ADI-R and ADOS), anxiety disorder, delayed language development, sat at 6 mo and walked at 12 mo, low average IQ (5%ile), health history uneventful except for asthma as an infant. When last evaluated at age 10 y, no obvious muscular difficulties were noted. This case also carries an intragenic duplication of IL1RAPL1, involved in XLID.","Mother unaffected"]
["4356_1","M","Familial","European","Stage 2","Blood","Xp11.4","X:38001148-38346471",345324,"Gain","OTC, RPGR, TSPAN7","Maternal (X-linked in a male)","no validation attempted","(not tested)","Uncertain-likely benign","Duplication of RPGR, OTC, and TSPAN7; similar duplication observed in an AGP male control. Mutations and deletions of OTC cause ornithine transcarbamylase deficiency; no cases have been reported with a duplication. TSPAN7 partial duplication; mutations and deletions cause XLID, duplications are found in healthy controls","Autism (based on medical history and ADI-R), language delay (first words 12 mo, first phrases 36 mo), PIQ 97, FSIQ 52","N/A"]
["4152_1","M","Sporadic","European","Stage 2","Blood","Xp11.4","X:40260354-40372806",112453,"Gain","ATP6AP2, CXorf38, LOC347411","Maternal (X-linked in a male)","no validation attempted","(not tested)","Uncertain","Duplication encompassing 3 genes, including ATP6AP2; ATP6AP2 silent mutation affecting splicing described in XLID with epilepsy","Autism (based on medical history and ADI-R), language delay, developmental delay, mild ID (Vineland Adaptive Behavior Composite score 64 at 4 y), sleep disturbance, oppositional defiant disorder, allergies, asthma, high cholesterol, irritable bowel syndrome, possible history of seizures, severe self-injurious behavior, multiple hospitalizations for respiratory illness and pneumonias during infancy, history of recurring ear infections; dysmorphic features (long philtrum, narrowed pointed nose, posteriorly rotated ears, prominent occiput, epicanthal folds, overlapping toes), hypotonia","Mother chronic cytomegalovirus infection, anxiety disorder, depression, migraines, anorexia, bulimia, articulation problems; father bipolar disorder, drug addiction, history of psychiatric hospitalization, high cholesterol"]
["3240_3","M","Familial","European","Stage 1","Buccal","Xp11.3","X:44706702-44919064",212363,"Gain","CXorf36, KDM6A","Maternal (X-linked in a male)","no validation attempted","(not tested)","Uncertain","Duplication of 2 genes, partially overlapping KDM6A, significance unknown; KDM6A mutations and deletions cause X-linked Kabuki syndrome","Autism (ADI-R and ADOS positive), language delay (first words 23 mo, first phrases 55 mo), articulation difficulties at age 5 y, verbal, PPVT-IV VIQ 88; has average verbal and non verbal ability but attends specialist schooling. No regression. Continued episodes of eneuresis at 7 y 8 m. No physical examination abnormalities. ","Father: social communication difficulties and perfectionism as child and adult; reading and spelling difficulties as a child; pragmatic difficulties as an adult. Mother: some social communication difficulties, shy, not chatty or so interested in conversation in childhood."]
["14314_4310","M","Sporadic","European","Stage 2","Blood","Xq13.1","X:70865247-71509736",644490,"Gain","CITED1, CXorf49, CXorf49B, ERCC6L, FLJ44635, FLJ46446, HDAC8, LOC100132741, NHSL2, PIN4, RGAG4, RPS26P11, RPS4X","Maternal (X-linked in a male)","qPCR","(not tested)","Uncertain","644 kb duplication encompassing 13 genes, partially overlapping HDAC8; mutations described recently in Cornelia de Lange syndrome and XLID resembling Wilson-Turner syndrome; similar partial duplication of HDAC8 observed in a male AGP control","Autism on ADI-R and ADOS, language delay, verbal, normal IQ (Griffiths 7 y 10 mo: language DQ 96, performance DQ 98, global DQ 100), no dysmorphic features or other anomalies, normal neurological exam, normal growth, no epilepsy. Negative family history","Mother unaffected"]
["1348_301","M","Familial","Other ","Stage 1","CL","Xq28","X:147163528-147758700",595173,"Gain","AFF2","Maternal (X-linked in a male)","qPCR","no CNV in sister with autism","Uncertain","AFF2 partial duplication; involved in XLID through trinucleotide expansion or deletion","Autism (based on ADI-R and ADOS), language delay (first words at 46 m), Vineland Adaptive Behavior Composite score 61. Phototherapy for hyperbilirubinemia after birth. Epilepsy and attention deficit disorder diagnosed at 5-6 y, depression diagnosed at 7 yo, physical aggression toward others, sensory abnormalities. Febrile seizures and complex partial seizures, EEG at 5 yo showed rolandic spikes, frequent seizures, treated with depakote. Physical exam: hyperpigmented area on face, hypertelorism, epicanthal folds, low nasal bridge, scoliosis, 5th finger clinodactyly on both hands, café-au-lait spot, mirror movements with finger tapping (AGRE ID AU0922301)","Father depression; mother depression, migraines, bulimia, and obsessive-compulsive traits"]
["5036_4","M","Familial","European","Stage 1","CL","Xq28","X:148075334-148617551",542218,"Gain","CXorf40A, HSFX1, HSFX2, IDS, LOC100131434, MAGEA11, MAGEA9, MAGEA9B, TMEM185A","Maternal (X-linked in a male)","no validation attempted","1 sister with Asperger, 2 unaffected dizygotic triplet brothers, and 1 unaffected sister tested with 1M array: only 1 unaffected triplet brother (5036_6) carried the duplication, no CNV in the other siblings","Uncertain-likely benign","542 kb duplication encompassing 9 genes, including IDS; mutations and deletions of IDS cause mucopolysaccharidosis type II; IDS duplication reported in unaffected males. Although duplication of IDS is not expected to be pathogenic, the contribution of the other genes in the interval is unknown. Gain also present in unaffected dizygotic triplet brother; CNV unlikely to be pathogenic","Autism (based on ADI-R and ADOS), average non-verbal IQ (32%ile), below average language (1%ile), no epilepsy, no dysmorphic features; triplet with 2 non-ASD brothers\n","Mother unaffected"]
["4354_1","M","Sporadic","European","Stage 2","Blood","Xq28","X:148344051-148707925",363875,"Gain","CXorf40A, HSFX1, HSFX2, IDS, LOC100131434, MAGEA11, MAGEA9, MAGEA9B, TMEM185A","Maternal (X-linked in a male)","no validation attempted","(not tested)","Uncertain-likely benign","363 kb duplication encompassing 9 genes, including IDS; mutations and deletions of IDS cause mucopolysaccharidosis type II; IDS duplication reported in unaffected males. Although duplication of IDS is not expected to be pathogenic, the contribution of the other genes in the interval is unknown. The presence of a similar duplication in the healthy brother of another AGP proband (see above) suggests this CNV is unlikely to be pathogenic","Autism (ADI-R and ADOS positive), language delay (first words 60 mo, first phrases 120 mo), verbal, moderate ID (PIQ 36)","N/A"]
["4166_1","M","Sporadic","European","Stage 2","Blood","Xq28","X:151620401-151805387",184987,"Gain","CETN2, CSAG1, CSAG2, CSAG3, MAGEA12, MAGEA2, MAGEA2B, MAGEA3, MAGEA6, NSDHL","Maternal (X-linked in a male)","no validation attempted","(not tested)","Uncertain","Xq28 duplication encompassing 10 genes, including NSDHL; mutations and deletions of NSDHL cause XLID (CK syndrome and CHILD syndrome); similar duplication including NSDHL in a male AGP control","ASD (based on medical history and ADI-R, missed criteria by one point on repetitive domain), verbal but history of language delay, borderline ID (Vineland Adaptive Behavior Composite score 72 at 7 y); history of ear infections, inguinal hernia, hydrocele; normal physical exam","Mother inguinal hernia; father unaffected"]
["Other CNV of uncertain clinical significance"]
["9877_204","M","Sporadic","Other ","Stage 2","Blood","1p21.3-p21.2","1:98247355-99645560",1398206,"Gain","LOC100129620, LPPR4, LPPR5, MIR137, SNX7","De novo","qPCR","(3 siblings, not tested)","Uncertain","1.4 Mb de novo 1p21 duplication (5 genes, including LPPR4 and MIR137). No similar CNV described. Overexpression of miR-137 inhibits dendritic morphogenesis, phenotypic maturation, and spine development both in brain and cultured primary neurons (Smrt et al. 2010). LPPR4, also called PRG-1 (plasticity-related gene 1), encodes a protein involved in axon growth during development; LPPR4 is specifically expressed in neurons. (see MIR137 in Highlighted genes in the Supplement)","Autism (autism on ADI-R and ADOS), language delay (first words 36 mo, first phrases 60 mo), functional language, mild ID (WISC-R at 11 y: VIQ 51, PIQ 80, FSIQ 64), normal height and head circumference, weight –1.6 SD, no dysmorphic features, normal physical exam, no epilepsy","Both parents healthy"]
["14310_4270","M","Sporadic","European","Stage 2","Blood","1p21.1","1:105623065-105795181",172117,"Gain","—","De novo","qPCR","(not tested)","Uncertain","Rare de novo non-genic duplication","Autism (meets criteria for autism on ADI-R and ADOS), language delay, no functional language, borderline impaired (Griffiths: language DQ 43, performance DQ 78, global DQ 70), no epilepsy","N/A"]
["14310_4270","M","Sporadic","European","Stage 2","Blood","1p21.1","1:105896243-106480692",584450,"Gain","—","De novo","qPCR","(not tested)","Uncertain","Rare de novo non-genic duplication","(see above)","N/A"]
["13082_963","M","Sporadic","European","Stage 1","Blood","2p25.1","2:11712589-11741036",28448,"Gain","NTSR2","De novo","qPCR","(not tested)","Uncertain","Rare de novo duplication of NTSR2 (whole)","Autism, verbal, normal IQ","N/A"]
["5089_5","M","Familial","Other","Stage 1","CL","2q12.1","2:102292943-102345460",52518,"Loss","IL1RL1","De novo","qPCR","monozygotic twin with autism also carries CNV (1 sister with ASD, no DNA)","Uncertain","Rare de novo deletion of IL1RL1","Autism (based on ADI-R and ADOS), severe ID (unable to complete IQ measure), below average language, aplastic kidney removed, no dysmorphic features, no epilepsy","N/A"]
["4260_1","M","Sporadic","European","Stage 2","Blood","2q14.2","2:119603876-119882278",278403,"Gain","C1QL2, C2orf76, DBI, STEAP3","De novo","qPCR","(no siblings)","Uncertain","Rare de novo duplication of 278 kb encompassing 4 genes, including C1QL2 (complement component 1, q subcomponent-like 2). Many members of the C1q family are secreted and play crucial roles in intercellular signaling. The Cbln (precerebellin) and C1q-like (C1ql) subfamilies are highly and predominantly expressed in the CNS. Cbln regulates synapse development and synaptic plasticity of excitatory synapses in the cerebellum.","Autism (based on medical history and ADI-R), developmental delay (walked at 21 mo), mild ID, speech disorder, ADHD, psychosis, suicide threats, bilateral 5th finger clinodactyly, curving of toes 3-4, occipital and facial flattening, macrocephaly, mild obesity, respiratory syncytial virus (RSV) infection at 5 mo (reported in Griswold et al. 2012a; family 17113)","Mother unaffected; father alcoholism, drug addiction, heart attack"]
["14414_5230","M","Sporadic","European","Stage 2","CL","2q36.3","2:230486629-230547253",60625,"Loss","FBXO36, TRIP12","De novo","qPCR","(not tested)","Uncertain","Rare de novo deletion of 2 genes, FBXO36 and TRIP12. TRIP12 is a candidate gene (see Highlighted genes in Supplement)","Autism (ADI-R and ADOS positive), no language delay (first words 12 mo, first phrases 24 mo), verbal; Griffiths at 5 y 9 mo: language DQ 87, performance DQ 78, global DQ 79","N/A"]
["14281_4040","M","Sporadic","European","Stage 1","Blood","3p26.3","3:2365612:2875100",509489,"Loss","CNTN4","Paternal","(no validation attempted)","(not tested)","Uncertain","Rare CNTN4 deletion, paternal. CNTN4 encodes contactin 4, a cell adhesion molecule involved in neuronal network formation and plasticity. This gene has been proposed as a candidate for the neurobehavioral manifestations of the 3p deletion syndrome, but the evidence remains inconclusive.","Autism (based on ADI-R and ADOS), language delay, no functional language, borderline IQ (Griffiths: language DQ 36, performance DQ 78, global DQ 70), no epilepsy","N/A"]
["5269_3","M","Sporadic","European","Stage 1","Blood","3p26.3","3:2644708-2876647",231940,"Gain","CNTN4","Paternal","qPCR, Illumina 1M-duo for sib","present in 1 non-ASD brother","Uncertain","Rare CNTN4 intragenic duplication, exonic, paternal (see above)","Autism (based on ADI-R and ADOS), delayed language development but average language (53%ile), above average IQ, no dysmorphic features, no epilepsy","Father ADHD"]
["3616_3","M","Uknown","European","Stage 2","Blood","3p25.3","3:9474320-9498362",24043,"Loss","SETD5","De novo","qPCR","(1 non-ASD younger brother, not tested)","Uncertain","Rare de novo SETD5 deletion. Several de novo deletions encompassing SETD5 described in subjects with ID; could play a role in the neurocognitive phenotype of the 3p deletion syndrome (Kellogg et al. 2013); de novo loss-of-function mutation in a subject with language delay and ID (Rauch et al., 2012). SETD5 is predicted to be a methyltransferase. NSD1 (Sotos syndrome) and EHMT1 (Kleefstra syndrome), implicated in ID and ASD, are histone methyltransferases (see Highlighted genes in the Supplement)","Autism (autism on both ADI-R and ADOS), language delay (first words 24 mo), verbal, borderline IQ (WISC-III: VIQ 64, PIQ 82, FSIQ 70). Born at term after normal pregnancy and delivery; no feeding or sleep problems; body length and head circumference during the first year of life were consistently between 0 to –1 SD; walked at 15 months; normal vision and hearing; had sensory-integration training because of over and undersensitivity; asthma and hay fever, no other medical issues, no seizures. Concerns about ADHD-like behavior in childhood, but did not fulfill criteria for ADHD and there are no concerns about hyperactivity at present. At 16 y, normal height and weight (50%ile), no obvious dysmorphic features (in particular, no ptosis, normal ears, no depressed nasal bridge, no long or prominent philtrum, no thin upper lip vermillion), normal fingers and toes.","Both parents unaffected"]
["5220_3","F","Sporadic","European","Stage 1","Blood","3p24.3","3:19127998-19640299",512302,"Gain","KCNH8","De novo","qPCR, Agilent 1M","(1 non-ASD maternal half-sister, no DNA)","Uncertain","Rare de novo duplication of KCNH8 (whole)","ASD (based on ADI-R and ADOS), no language delay, average IQ; born with asymmetric head, fontanelle closed at age 4 y; dysmorphic features, no epilepsy","N/A"]
["3174_3","M","Familial","European","Stage 1","Blood","3p24.3","3:19921061-20096832",175772,"Loss","C3orf48, EFHB, KAT2B, RAB5A","De novo","Agilent 1M (SNP array indicated mosaicism)","absent in 1 brother with autism","Uncertain","Rare de novo deletion of 4 genes","Autism on ADI-R and ADOS, low average IQ, language delay, some gross and fine motor coordination difficulties, no dysmorphic features or associated medical or psychiatric problems, no epilepsy. This case also carries a paternally-inherited 16p12.1 microdeletion","Evidence of broader autism phenotype (social and communication domains) in both parents, with father scoring higher"]
["20032_1226001","M","Familial","European","Stage 2","Blood","3q12.3,3q12.2,3q13.11","3:101854561-106110833",4256273,"Loss","ABI3BP, CEP97, FAM172BP, FAM55C, GPR128, IMPG2, LOC100009676, LOC152225, LOC285359, NFKBIZ, PCNP, RG9MTD1, RPL24, SENP7, TFG, ZBTB11, ZPLD1","Maternal","qPCR","deletion present in affected brother (20032_1226021) and affected sister (20032_122602), both with broad autism spectrum","Uncertain","4.2 Mb 3q12-q13 deletion (17 genes), maternal; unique","Autism on ADI-R and ADOS, low average IQ (83), no language delay but language testing at 7 y 2 mo gave scores significantly below overall IQ; no dysmorphic features, normal head circumference; sleep problems; no seizures. Affected brother 20032-1226021 also carries the deletion: delayed language, social difficulties but not clearly consistent with autism diagnosis; tested at age 3 y 1 m, doesn't meet criteria for autism on ADI-R (social 12, non-verbal communication 6, repetitive behavior 1, age abnormality 5) or ADOS (module 1, communication 3, social 3). Differential Ability Scales NVIQ 86, FSIQ 72. No dysmorphic features, normal head circumference and height; odd gait, poor balance; sleep problems; no seizures. Mother took fluoxetine and valproate during pregnancy. Affected sister 20032-1226022 also carries the deletion; tested at 5 y 2 mo, doesn't meet criteria for autism on ADI-R (social 9, communication 4, repetitive behavior 7, age abnormality 2) or ADOS (social 1, communication 0). Differential Ability Scales VIQ 94, NVIQ 101, FSIQ 95. No dysmorphic features, normal head circumference; sleep problems; no seizures. Mother took fluoxetine during pregnancy. ","Mother: ADHD, anxiety and depression. Adult SRS total 51; normal IQ (102); facial tics, apparent auditory processing difficulties; reported spelling learning disabilities; severe constipation. Mother reported family history of depression on both sides of her family, and maternal family history of OCD."]
["5245_3","M","Familial","European","Stage 1","CL","3q13.31","3:117285007-117477191",192185,"Loss","LSAMP","De novo","qPCR, Agilent 1M (seems mosaic)","1 sister with ASD, no CNV","Uncertain","Rare de novo partial mosaic deletion of LSAMP; the deletion was present in 50% of the subject's cells, calculated using the B deviation (deviation from the expected BAF value of 0.5 for heterozygous SNPs) (Rodriguez-Santiago et al. 2010) (see Highlighted genes in the Supplement)","Autism (based on ADI-R and ADOS), language delay, below average non-verbal IQ (<1%ile), below average language (1%ile), apraxia, abnormal sleep EEG without seizures; born at 29 wks, intraventricular hemorrhage, mild cerebral palsy; alopecia areata, no dysmorphic features","N/A"]
["8587_210","F","Uknown","European","Stage 2","Blood","3q22.3","3:139760896-140127703",366808,"Gain","CEP70, FAIM, PIK3CB","De novo","qPCR","(not tested)","Uncertain","Rare de novo duplication of PIK3CB and 2 other genes. This CNV is likely to increase PIK3CB expression, leading to excessive phosphatidylinositol 3-kinase (PI3K) activity. PI3K, which is regulated by FMRP (Ascano et al., 2012), is elevated in Fragile X syndrome mouse knockouts (Gross et al., 2010; Sharma et al., 2010), and down-regulation of this pathway has been shown to have therapeutic effect in ASD/FXS mouse models by rescuing several FXS phenotypes (see Highlighted genes in the Supplement)","Autism (ADI-R and ADOS positive), no language delay (first words 10 mo, first phrases 12 mo), verbal, average IQ (WISC-III at 13 y 9 mo: VIQ 92, PIQ 78, FSIQ 84)","N/A"]
["8588_201","M","Unknown (autistic traits in father and paternal uncle)","European","Stage 2","Blood","3q29","3:195971510-197675831",1704322,"Loss","ACAP2, APOD, C3orf21, LOC100507391, LOC401109, MIR570, MUC20, MUC4, OSTalpha, PCYT1A, PPP1R2, SDHAP1, SDHAP2, TCTEX1D2, TFRC, TM4SF19, TM4SF19-TCTEX1D2, TNK2, UBXN7, ZDHHC19","De novo","qPCR","(no siblings)","Uncertain","1.7 Mb de novo deletion, 27% overlap of the 3q29 microdeletion syndrome region; does not include the candidates genes for the syndrome PAK2 and DLG1. No similar deletions reported","Autism on ADI-R and ADOS, no language delay, hypotonia during childhood, sleep disorder, average IQ (WISC-III at 14 y: VIQ 87, PIQ 78, FSIQ 81), no epilepsy","Father socialization difficulties and rigidity; mother healthy"]
["8677_201","M","Sporadic","Other","Stage 2","Blood","4q22.2","4:94659049-95289667",630619,"Gain","ATOH1, GRID2","De novo","qPCR","(not tested)","Uncertain","Rare de novo duplication of ATOH1 and GRID2","Autism (ADI-R and ADOS positive), no language delay (first words 13 mo, first phrases 30 mo), verbal, Differential Ability Scales at 6 y: FSIQ 66","N/A"]
["6402_3","M","Sporadic","European","Stage 2","Unknown (blood or CL)","4q22.3-q23","4:98781694-99627129",845436,"Gain","C4orf37, RAP1GDS1, TSPAN5","De novo","qPCR","(3 siblings, no DNA)","Uncertain","845 kb de novo duplication (3 genes, including TSPAN5). Similar duplication in a case from ISCA (nssv581168) with global developmental delay (inheritance unknown). TSPAN5 belongs to the tetraspanin family, which encodes proteins that increase cell motility, modulate proliferation, promote differentiation and facilitate synapse formation","Autism, language delay (first words 24 mo, first phrases 60 mo), functional language, borderline intellectual functioning (WISC III: VIQ 73, PIQ 80, FSIQ 74), no dysmorphic features, no epilepsy, normal brain MRI","Both parents depression"]
["6033_3","M","Familial","European","Stage 1","Blood","5p14.3","5:19532212-20357961",825750,"Loss","CDH18","Maternal","qPCR","absent in 1 sister with autism and ID","Uncertain","Rare CDH18 exonic deletion, maternal. CDH18 encodes cadherin 18, which is expressed in the mouse developing brain and is likely to be involved in synapse formation and axonal growth and guidance","High-functioning autism, early speech development, above average IQ (WISC-R FSIQ 127), prolonged jaundice after birth, umbilical hernia, neonatal hypothyroidism, normal physical exam, no epilepsy","Both parents are healthy but have some Asperger traits"]
["8709_201","F","Sporadic","European","Stage 2","Blood","5q14.3","5:88588170-89505509",917340,"Loss","MIR3660","De novo","qPCR","no CNV in unaffected sister","Uncertain","Rare de novo deletion of MIR3660","Autism (ADI-R and ADOS positive), language delay (first words 48 mo, first phrases 54 mo), verbal, Vineland at 8 y 8 mo: Communication 50, Daily Living Skills 50, Socialization 61, Adaptive Behavior Composite 50","N/A"]
["18133_302","M","Sporadic","European","Stage 2","CL","6q12-q13","6:69540429-73375020",3834592,"Gain","B3GAT2, BAI3, C6orf155, C6orf57, COL19A1, COL9A1, FAM135A, LMBRD1, MIR30A, MIR30C2, OGFRL1, RIMS1, SMAP1","De novo","qPCR","(2 non-ASD siblings, not tested)","Uncertain","3.8 Mb de novo 6q12q13 duplication (13 genes, including RIMS1). RIMS1 is involved in learning and memory in knock-out mice and is an ASD candidate gene (de novo frameshift variant in ASD exome study, Iossifov et al. 2012). A missense mutation in RIMS1 was reported in a 4-generation family with autosomal dominant cone-rod dystrophy. The protein encoded by this gene is a RAS gene superfamily member that regulates synaptic vesicle exocytosis; expressed in brain and retina.","Autism (based on ADI-R and ADOS), single words at 22 mo, no phrases at 8 y 10 mo (age at ADI), language regression at 30 mo, duration of loss 24 mo, definite loss of social engagement/responsiveness skills at 27 mo; Stanford Binet VIQ 43, NVIQ 42, FSIQ 40; PPVT 20 (receptive vocabulary functioning extremely low); sensory abnormalities, hand/finger mannerisms, stereotyped body movements, odd gait (toe-walking, touching foot to leg with each step), physical aggression toward others, slight/occasional self-injury, no evidence of seizures (AGRE ID: AU2117302)","Mother bipolar disorder; father language delay (no words until 3 yo), possible Asperger syndrome but no testing done. Two siblings, not tested for CNV: unaffected brother had articulation problems and speech/language therapy. Unaffected dizygotic twin sister, evaluated with ADI-R and ADOS for research study, both were negative."]
["6248_3","M","Sporadic","European","Stage 2","Unknown (blood or CL)","6q14.3","6:86352577-86376159",23583,"Loss","SNX14, SYNCRIP","De novo","qPCR","(2 sibs, no DNA)","Uncertain","Rare de novo partial deletion of SYNCRIP and SNX14. SYNCRIP is a candidate gene (see Highlighted genes in Supplement)","Autism, non-verbal, severe ID; born by C-section with increased height and head circumference; at 15 y: height >+ 3 SD, macrocephaly (head circumference >+3 DS) (his unaffected father and 2 brothers are also tall and have macrocephaly); long and narrow hands and feet, normal neurological exam, 2 café-au-lait spots; 1 absence seizure at 11 y, with abnormal EEG, probably related to medications taken at that time, no other seizures afterwards","Both parents unaffected"]
["6164_3","F","Sporadic","European","Stage 1","Unknown (blood or CL)","6q25.3","6:160023074-160081618",58545,"Gain","SOD2, WTAP","De novo","qPCR","(1 healthy sister, no DNA)","Uncertain","Rare de novo partial duplication of SOD2 and WTAP","Autism, language delay, mild ID, normal physical exam, normal brain MRI","Mother unaffected, breast cancer; father unaffected"]
["8612_201","M","Unknown","European","Stage 2","Blood","6q26","6:162588879-162629938",41060,"Loss","PARK2","De novo","qPCR","(not tested)","Uncertain","Rare de novo intragenic deletion of PARK2","Autism (ADI-R and ADOS positive), no language delay (first words 21 mo, first phrases 30 mo), verbal, WASI at 19 y: VIQ 100, PIQ 100, FSIQ 100","N/A"]
["3164_3","M","Familial","European","Stage 1","CL","7p21.1","7:18450792-18490822",40031,"Loss","HDAC9","Paternal","qPCR","1 brother with autism, no CNV","Uncertain","Rare deletion of HDAC9 (histone deacetylase 9); several other inherited deletions in databases; 3 schizophrenia cases with exonic HDAC9 deletions among 3391 cases (inheritance unknown); no deletions in 3181 controls (Lang et al. 2012) (see Highlighted genes in the Supplement)","Proband (3164-3): autism (ADI-R and ADOS positive), language delay (first words 54 mo, first sentences 60 mo), phrase speech at 6 y 9 mo, verbal, average performance ability, lower verbal ability (PPVT-III at 6 y 10 m: VIQ 67). Not continent at 6 y 9 mo; some gross and fine motor difficulties; suggestion of episodes that may have been seizures, but no definite diagnosis.\nBrother (3164-4), no CNV: autism, Mullen performance IQ 50 verbal IQ 25, low Vineland age equivalents across all domains. No words or phrases at 4 years.","N/A"]
["1960_301","F","Familial","European","Stage 1","CL","7q22.1","7:102699832-102798745",98914,"Loss","DNAJC2, DPY19L2P2, PMPCB, PSMC2, SLC26A5","De novo","Illumina 550K (Glessner et al. 2009)","(not tested)","Uncertain","Rare de novo deletion of 5 genes","Autism by ADI-R and ADOS, verbal, ID, floppy infant, gastrointestinal problems (AGRE ID AU1558301)","N/A"]
["5370_3","M","Sporadic","European","Stage 1","Blood","7q36.2","7:153775586-153844747",69162,"Loss","DPP6","De novo","qPCR, Affy 500K (Marshall et al. 2008), Agilent 1M","(no siblings)","Uncertain","Rare de novo intragenic deletion of DPP6","Autism (based on ADI-R and ADOS), no dysmorphic features, no epilepsy, normal brain CT","N/A"]
["5290_3","M","Sporadic","Other","Stage 1","Blood","8p23.3","8:704383-1521910",817528,"Gain","DLGAP2, LOC286083","De novo","qPCR, Affy 500K (Marshall AJHG 2008), Agilent 1M","1 brother with ASD features, no CNV by qPCR","Uncertain","Rare de novo duplication of 2 genes, including partial duplication of DLGAP2","Autism (based on ADI-R and ADOS), unable to complete IQ measure, below average language (1%ile), no dysmorphic features, no epilepsy","N/A"]
["1142_4","F","Familial","European","Stage 1","CL","8q11.21","8:48631388-48802529",171142,"Gain","KIAA0146","De novo","Affy 5.0 (Bucan et al. 2009) ","(not tested)","Uncertain","Rare de novo intragenic duplication of KIAA0146","Autism by ADI-R and ADOS, verbal, normal IQ, seizures, gastrointestinal problems (AGRE ID AU035004)","N/A"]
["6321_3","M","Sporadic","European","Stage 1","Unknown (blood or CL)","8q12.3-q13.1","8:65354366-66254869",900504,"Loss","BHLHE22, CYP7B1, LOC100130155, LOC401463, MIR124-2","De novo","qPCR","(2 healthy sisters, no DNA)","Uncertain","900 kb de novo 8q12.3-q13.1 deletion (5 genes, including BHLHE22). One similar de novo deletion in ISCA. BHLHE22 belongs to the basic helix-loop-helix (bHLH) family of transcription factors that regulate cell fate determination, proliferation, and differentiation; expressed exclusively in the central nervous system and retina","Autism, language delay, mild ID, no dysmorphic features, flat feet, normal neurological exam","Both parents unaffected"]
["8500_201","M","Familial","European","Stage 2","Blood","8q21.11","8:74692898-74967280",274383,"Loss","STAU2, UBE2W","De novo","qPCR","(not tested)","Uncertain","Rare de novo deletion of 2 genes, STAU2 and UBE2W. UBE2W encodes a nuclear-localized ubiquitin-conjugating enzyme (E2)","Autism (ADI-R, ADOS, and clinical diagnosis), high IQ (WISC-III at 14 y: VIQ 117, PIQ 125, FSIQ 124), head circumference 1.4 SD, height –0.35 SD, no dysmorphic features, no epilepsy","Both parents have normal IQ"]
["8559_201","F","Sporadic","European","Stage 2","Blood","8q21.13","8:82090958-83921979",1831022,"Loss","CHMP4C, FABP12, FABP4, FABP5, FABP9, IMPA1, PAG1, PMP2, SLC10A5, SNX16, ZFAND1","Paternal","qPCR","(not tested)","Uncertain","1.8 Mb 8q21 deletion (11 genes), paternal, unique","Autism on ADI-R and ADOS, comorbid OCD; VIQ 91, PIQ 76, FSIQ 83 at age 23; history of ABO incompatibility with blood transfusion at birth; overweight at age 34, normal height and head circumference, no epilepsy","Mother dyslexia and drug abuse, father unaffected"]
["5032_4","M","Familial","European","Stage 1","Blood","9p24.3","9:98998-334508",235511,"Loss","C9orf66, CBWD1, DOCK8, FOXD4","De novo","qPCR","1 sister with ASD, no CNV","Uncertain","Rare de novo deletion of 4 genes, including DOCK8","Autism (based on ADI-R and ADOS), above average non-verbal IQ, below average language, history of seizures, no dysmorphic features","N/A"]
["6246_4","M","Sporadic","European","Stage 1","Unknown (blood or CL)","9p23","9:9399606-9631169",231564,"Loss","PTPRD","De novo","qPCR","absent in 1 healthy sister","Uncertain","Rare de novo intragenic deletion of PTPRD","Autism, no language delay, mild ID, neonatal hypotonia, marfanoid habitus, arachnodactylia","Both parents unaffected"]
["16089_1571115001","M","Sporadic","European","Stage 2","CL","9q22.33","9:100940231-100952579",12349,"Loss","TGFBR1","Maternal","qPCR ","(unaffected sib not tested)","Uncertain","TGFBR1 exonic deletion. Mutations cause Loeys-Dietz syndrome; no deletions reported","Autism (ADI-R and ADOS positive), language delay, uses few words; borderline IQ (Leiter-R Brief at 11 y 9 mo: PIQ 73)","Mother bipolar, father OCD-like"]
["14237_2650","M","Sporadic","European","Stage 1","Blood","9q31.1","9:103456776-107140273",3683498,"Loss","ABCA1, CYLC2, GRIN3A, LOC286367, NIPSNAP3A, NIPSNAP3B, OR13C2, OR13C3, OR13C4, OR13C5, OR13C8, OR13C9, OR13D1, OR13F1, SLC44A1, SMC2","De novo","qPCR","(not tested)","Uncertain-likely pathogenic","3.6 Mb de novo deletion encompassing 16 genes, including GRIN3. This gene encodes a subunit of NMDA receptors and might be involved in the development of dendritic spines. Several genes encoding NMDA receptor subunits have been involved in ASD and/or ID (GRIN2A, GRIN2B) ","ASD diagnosis, ADI-R and ADOS positive, walked at 15 months, first words 12 months, first phrases 24 months, average IQ (WISC: VIQ 93, PIQ 98, FSIQ 93), no dysmorphic features, no neurological abnormalities, normal growth, no epilepsy","N/A"]
["14417_5260","M","Sporadic","European","Stage 2","CL","9q33.1","9:117311405-117727764",416360,"Loss","C9orf27","De novo","qPCR","(not tested)","Uncertain","Rare de novo partial deletion of C9orf27","Autism on ADI-R, ASD on ADOS, language delay (first words 42 mo, first phrases 48 mo), verbal, Griffiths at 3 y 7 mo: language DQ 55, performance DQ 102, global DQ 74","N/A"]
["9756_201","M","Sporadic","Other","Stage 2","Blood","9q34.12","9:132572435-132597937",25503,"Loss","ABL1","De novo","qPCR","(not tested)","Uncertain","Rare de novo partial deletion of ABL1","Autism (ADI-R and ADOS positive), no language delay (first words 10 mo, first phrases 14 mo), limited language, Leiter-R Brief at 4 y 7 mo: PIQ 80","N/A"]
["18116_302","M","Familial","European","Stage 2","CL","10p11.23","10:29797497-31133591",1336095,"Gain","KIAA1462, LOC729668, LYZL2, MAP3K8, MIR604, MIR938, MTPAP, SVIL","Unknown (not maternal)","qPCR","no CNV in affected sib","Uncertain","1.3 Mb duplication (8 genes), inheritance unknown (not maternal). 1 case in DECIPHER with ID/developmental delay has a smaller duplication in the same region. Genes involved in both duplications: LYZL2 (lysozyme-like gene expressed in testis, epididymis and placenta), MAP3K8 (oncogene, encodes a member of the serine/threonine protein kinase family), and MTPAP (defects in MTPAP cause autosomal recessive spastic ataxia type 4)","Autism (based on ADI-R and ADOS), language delay (first words 48 mo, first phrases 66 mo); PPVT 72; Stanford Binet: VIQ 52, NVIQ 86, FSIQ 67; odd gait (bouncing walk), significant aggression toward others, slight self-injury, EEG borderline abnormal, no reports of seizures (AGRE ID: AU2071302)","Mother had articulation problems; no other parent information"]
["18172_302","M","Sporadic","Other ","Stage 2","CL","10p11.21","10:34963905-35536952",573048,"Gain","CREM, CUL2, PARD3","De novo","qPCR","(1 unaffected dizygotic twin sister, not tested)","Uncertain","Rare de novo duplication encompassing 3 genes","Autism on ADI-R and ASD on ADOS, language delay (first words 36 mo, first phrases 48 mo), average IQ (Stanford Binet VIQ 87, NVIQ 100, FSIQ 93; PPVT 97); artificial insemination and fertility medications used for pregnancy (AGRE ID: AU2215302)","Both parents unaffected. Unaffected dizygotic twin sister, evaluated with ADI-R and ADOS for research study, both were negative."]
["14393_5020","M","Sporadic","European","Stage 2","CL","10q22.2","10:74801551-75278951",477401,"Loss","AGAP5, ANXA7, BMS1P4, CAMK2G, CHCHD1, FUT11, KIAA0913, MYOZ1, NDST2, PPP3CB, SEC24C, SYNPO2L, USP54, ZMYND17","De novo","qPCR","(not tested)","Uncertain","Rare de novo deletion of 477 kb (14 genes)","ASD on ADI-R and ADOS, language delay (first words 12 mo, first phrases 36 mo), verbal, Griffiths at 5 y 7 mo: language DQ 101, performance DQ 75, global DQ 84; seizures","N/A"]
["8549_201","M","Sporadic","European","Stage 2","Blood","11q14.3,11q14.2","11:85944331-87925352",1981022,"Loss","CTSC, FZD4, GRM5, ME3, PRSS23, RAB38, TMEM135","Paternal","qPCR","(1 healthy sister, not tested)","Uncertain","1.98 Mb 11q14 deletion (7 genes), paternal, rare","Autism on ADI-R and ADOS, average IQ (VIQ 101, PIQ 107, FSIQ 104); height and weight normal; front teeth protruding and conspicuous, no other dysmorphic features; astigmatism; fitted with splints for aberrant leg growth and mild deformation of hips at 18 mo; no epilepsy; brain CT at 8 y: mild dilatation of occipital horn of the left ventricle and mild atrophy in that region ","Father reading difficulty, may have social impairment; mother macular degeneration and mood disorder"]
["5272_3","M","Familial","Other","Stage 1","Blood","12q23.1","12:98445422-98540678",95257,"Loss","ANKS1B","De novo","qPCR, Agilent 1M, Illumina 1M-duo for sib","one brother with autism, no CNV","Uncertain","Rare de novo intronic ANKS1B deletion","Autism (based on ADI-R and ADOS), language delay (first words 42 mo, first phrases 48 mo), verbal, average IQ (Leiter PIQ 98), no epilepsy","N/A"]
["1050_3","F","Familial","European","Stage 1","CL","14q11.2","14:20279711-20345174",65464,"Gain","EDDM3A, EDDM3B, RNASE1, RNASE6","De novo","Illumina 550K (Glessner et al. 2009), Affy 5.0 (Bucan et al. 2009)","(not tested)","Uncertain","Rare de novo duplication of 4 genes","Autism by ADI-R and ADOS, verbal, no ID (AGRE ID AU013303)","N/A"]
["8638_201","M","Unknown","European","Stage 2","Blood","14q13.2","14:35203374-35369853",166480,"Loss","BRMS1L, RALGAPA1","De novo","qPCR","(not tested)","Uncertain","Rare de novo deletion of BRMS1L and RALGAPA1","Autism (ADI-R and ADOS positive), no language delay (first words 12 mo, first phrases 14 mo), verbal, WASI at 10 y 1 mo: VIQ 89, PIQ 100, FSIQ 94","N/A"]
["4272_1","M","Sporadic","European","Stage 2","Blood","14q23.2-q23.3","14:63824114-65347410",1523297,"Loss","AKAP5, C14orf50, CHURC1, CHURC1-FNTB, ESR2, FNTB, FUT8, GPX2, HSPA2, LOC645431, MAX, MTHFD1, PLEKHG3, RAB15, SPTB, TEX21P, ZBTB1, ZBTB25","De novo","qPCR","2 unaffected sibs, no CNV","Uncertain-likely pathogenic","1.5 Mb de novo 14q23.2q23.3 deletion (18 genes); no similar deletions reported","ASD (based on medical history), ADI-R and ADOS: autism; ADHD, speech language disorder (articulation problems), anxiety disorder, borderline mild ID (WISC at 8 y: VIQ 67, PR 108, WM 77, PS 65, FSIQ 75); had nuchal chord at birth and required oxygen; spherocytosis (deletion overlaps SPTB, involved in autosomal dominant spherocytosis), headaches, heart murmur, history of fifth disease (requiring 3 blood transfusions) and frequent ear and viral infections; macrocephaly, obese, no dysmorphic features, intention hand tremor; normal EEG (reported in Griswold et al. 2012b; family 17165) ","Mother anxiety/panic disorder, migraines, fibromyalgia; father bacterial meningitis, atrial fibrillation, heart murmur"]
["17009_1","M","Sporadic","European","Stage 2","CL","14q31.1","14:78575296-78596793",21498,"Loss","NRXN3","De novo","qPCR","(not tested)","Uncertain","Rare de novo intronic NRXN3 deletion","ASD (ASD on ADI-R, autism on ADOS), no language delay (first words 12 mo, first phrases 20 mo), verbal, no ID (PPVT-III VIQ 71, Raven's Matrices-colored PIQ 105), no epilepsy","N/A"]
["8117_202","M","Familial","European","Stage 2","Blood","15q11.2","15:19618993-20777695",1158703,"Loss","CYFIP1, GOLGA6L1, GOLGA8DP, LOC727924, NIPA1, NIPA2, OR4M2, OR4N3P, OR4N4, REREP3, TUBGCP5, WHAMML1","Maternal/Paternal","no validation attempted","(not tested)","Uncertain (likely risk factor)","Proximal 15q11.2 microdeletion between BP1 and BP2. Recurrent 15q11.2 deletions adjacent to the Prader-Willi/Angelman syndrome critical region (BP2-BP3) and encompassing 4 genes (TUBGCP5, CYFIP1, NIPA2 and NIPA1), have been shown to be enriched in idiopathic generalized epilepsy, schizophrenia, congenital heart disease and in clinical cohorts of neurodevelopmental disorders. The deletions are often inherited from normal or mildly affected parents and are also present in healthy controls at relatively high frequency, indicating variable expressivity/incomplete penetrance. No significant enrichment has been shown yet specifically in ASD, probably because very large samples of cases and controls are required to demonstrate a statistically significant effect for CNV playing a contributory rather than a causative role","Autism (ADI-R and ADOS positive), no language delay, verbal, moderate ID (WISC-III at 9 y 4 mo: VIQ 50, PIQ 50, FSIQ 42). This case also has a 15q11-q13 duplication syndrome","N/A"]
["4045_1","F","Familial","European","Stage 2","Blood","15q11.2","15:19767013-20778963",1011951,"Loss","CYFIP1, GOLGA6L1, GOLGA8DP, LOC727924, NIPA1, NIPA2, OR4M2, OR4N3P, OR4N4, REREP3, TUBGCP5, WHAMML1","Paternal","no validation attempted","(not tested)","Uncertain (likely risk factor)","Proximal 15q11.2 microdeletion between BP1 and BP2 (see above)","Autism (ADI-R and ADOS positive), language delay (first words 66 mo), verbal, Vineland at 8 y 6 mo: Communication 50,Daily Living Skills 32, Socialization 63, Adaptive Behavior Composite 45; seizures","N/A"]
["4541_1","M","Sporadic","European","Stage 2","Blood","15q11.2","15:20249841-20778963",529123,"Loss","CYFIP1, GOLGA6L1, GOLGA8DP, NIPA1, NIPA2, TUBGCP5, WHAMML1","Maternal","no validation attempted","(not tested)","Uncertain (likely risk factor)","Proximal 15q11.2 microdeletion between BP1 and BP2 (see above)","Autism (ADI-R and ADOS positive), language delay (first words 12 mo, first phrases 45 mo), verbal, VIQ 77, PIQ 61, FSIQ 65","N/A"]
["14358_4720","M","Sporadic","European","Stage 2","Blood","15q11.2","15:20301669-20773130",471462,"Loss","CYFIP1, NIPA1, NIPA2, TUBGCP5, WHAMML1","Maternal","no validation attempted","(not tested)","Uncertain (likely risk factor)","Proximal 15q11.2 microdeletion between BP1 and BP2 (see above)","ASD (ASD on ADI-R, autism on ADOS), language delay (first words 36 mo), limited language, Griffiths at 3 y 7 mo: language DQ 49, performance DQ 98, global DQ 90","N/A"]
["2288_1","M","Sporadic","European","Stage 2","Blood","15q11.2","15:20301669-20777695",476027,"Loss","CYFIP1, NIPA1, NIPA2, TUBGCP5, WHAMML1","Maternal","qPCR","(not tested)","Uncertain (likely risk factor)","Proximal 15q11.2 microdeletion between BP1 and BP2 (see above)","ASD (ASD on ADI-R, autism on ADOS), language delay, verbal, WPPSI-III at 5 y 7 mo: VIQ 75, PIQ 84, FSIQ 78","N/A"]
["8430_204","M","Sporadic (2 affected monozygotic twins)","Other ","Stage 2","Blood","15q11.2","15:20301669-20777695",476027,"Loss","CYFIP1, NIPA1, NIPA2, TUBGCP5, WHAMML1","De novo","qPCR","CNV in affected monozygotic twin, absent in unaffected brother","Uncertain (likely risk factor)","Proximal 15q11.2 microdeletion between BP1 and BP2 (see above)","ASD (autism on ADI-R, did not meet criteria for ASD on ADOS), language delay (first words 65 mo, first phrases 69 mo), verbal, WISC-III at 6 y: VIQ 56, PIQ 106, FSIQ 78","N/A"]
["4431_1","M","Sporadic","European","Stage 2","Blood","15q11.2","15:20303106-20778963",475858,"Loss","CYFIP1, NIPA1, NIPA2, TUBGCP5, WHAMML1","Paternal","no validation attempted","(not tested)","Uncertain (likely risk factor)","Proximal 15q11.2 microdeletion between BP1 and BP2 (see above)","Autism (ADI-R and ADOS positive), language delay, limited language, seizures","N/A"]
["5453_4","M","Familial (second cousin affected)","European","Stage 1","Blood","15q11.2","15:20303106-20836955",533850,"Loss","CYFIP1, GOLGA8IP, HERC2P2, NIPA1, NIPA2, TUBGCP5, WHAMML1","Paternal","qPCR, Agilent 1M, Illumina 1M-duo for sibs","2 non-ASD brothers, no CNV","Uncertain (likely risk factor)","Proximal 15q11.2 microdeletion between BP1 and BP2 (see above)","Autism (based on ADI-R and ADOS), language delay, low-functioning (unable to complete IQ measure), no dysmorphic features, no epilepsy","Both parents unaffected"]
["6319_3","M","Sporadic","European","Stage 1","Blood","15q11.2","15:20305097-20773130",468034,"Loss","CYFIP1, NIPA1, NIPA2, TUBGCP5, WHAMML1","Paternal","MLPA","(1 healthy brother, no DNA)","Uncertain (likely risk factor)","Proximal 15q11.2 microdeletion between BP1 and BP2 (see above)","PDD-NOS, language delay, functional language, mild ID, no epilepsy, hypermetropia, large and prominent ears, no other dysmorphic features, flat feet, normal brain MRI. This case also carries a de novo SHANK2 deletion ","Both parents healthy"]
["4060_1","M","Familial","European","Stage 2","Blood","15q11.2","15:20305097-20836955",531859,"Loss","CYFIP1, GOLGA8IP, HERC2P2, NIPA1, NIPA2, TUBGCP5, WHAMML1","Maternal","no validation attempted","(not tested)","Uncertain (likely risk factor)","Proximal 15q11.2 microdeletion between BP1 and BP2 (see above)","Autism (ADI-R positive), no language delay (first words 12 mo, first phrases 30 mo), verbal, moderate ID (Griffiths at 7 y 10 mo: performance DQ 36), seizures","N/A"]
["6101_4","M","Familial","Other","Stage 1","Unknown (blood or CL)","15q24.3","15:74735339-74929817",194479,"Loss","SCAPER","De novo","qPCR","absent in 1 brother with autism and 1 unaffected sister","Uncertain","Rare de novo intragenic deletion of SCAPER","Autism, language delay, articulation defect, moderate ID, normal physical exam","Both parents unaffected"]
["8695_201","M","Sporadic","European","Stage 2","Blood","15q25.2","15:81728085-82623936",895852,"Loss","ADAMTSL3, BNC1, LOC648809, SH3GL3","De novo","qPCR","(not tested)","Uncertain","900 kb de novo deletion, 40% overlap of the proximal 15q25.2 microdeletion syndrome region (ID locus). All reported deletions are larger.","Autism (ADI-R and ADOS positive), language delay (first words 42 mo, first phrases 48 mo), verbal, mild ID (Differential Ability Scales at 6 y: FSIQ 58)","N/A"]
["14181_2940","M","Sporadic","European","Stage 1","Blood","15q25.2","15:82906265-82985247",78983,"Gain","LOC100506874, SCAND2, UBE2Q2P1, ZSCAN2","De novo","qPCR","(1 healthy sibling not tested)","Uncertain","Rare de novo duplication encompassing 4 genes; the proximal half overlaps several segmental duplications","Autism (ADI-R and ADOS positive), speech delay (first words 36 mo, first phrases 48 mo), low average IQ (VIQ 88, PIQ 72, FSIQ 72); dysmorphic features: retrognathia; motor incoordination; no epilepsy","Both parents unaffected"]
["16058_1571037001","M","Familial","European","Stage 2","CL","16p13.3","16:2051231-2079696",28466,"Gain","PKD1, TSC2","Paternal","qPCR","(brother with autism and seizures and 2 sisters with no diagnosis, not tested)","Uncertain","TSC2 partial duplication; mutations and deletions cause tuberous sclerosis","Autism, few words, moderate ID (Leiter Brief at 24 y: PIQ 40), chronic otitis media, no seizures; no problems at birth but large baby (4.59 kg)","Both parents unaffected"]
["14071_1240","M","Sporadic","European","Stage 1","Blood","16p12.1 ","16:21788416-22351124",562709,"Loss ","EEF2K, C16orf65, CDR2, POLR3E, C16orf52, UQCRC2, VWA3A","Paternal","qPCR","(not tested)","Uncertain (likely risk factor)","Recurrent 16p12.1 microdeletions have been associated with neurodevelopmental disorders; cases with such deletions are more likely than controls to carry an additional large CNV, supporting a “two-hit” model for severe developmental delay (Girirajan et al. 2010). Most deletions are inherited, and have been reported in controls at a higher frequency compared to other clinically relevant CNV, suggesting not only variable expressivity/incomplete penetrance but also a weaker role as risk factors","Autism (meets criteria for autism on ADI-R), language delay (first words 36 mo), no functional language, mild ID (Griffiths: language DQ 43, performance DQ 70, global DQ 56), no epilepsy","N/A"]
["6261_3","M","Sporadic","European","Stage 1","Blood","16p12.1","16:21854731-22331199",476469,"Loss","EEF2K, PDZD9, CDR2, POLR3E, C16orf52, UQCRC2, VWA3A ","Maternal","qPCR","(2 healthy sibs, no DNA)","Uncertain (likely risk factor)","Rare recurrent 16p12.1 microdeletion (see above)","Autism, language delay, verbal, mild ID; hearing deficit detected at 1 y, treated with hearing aid, audiogram at 4 yrs normal; normal physical exam, no epilepsy, normal brain CT","Both parents unaffected"]
["3174_3","M","Familial","European","Stage 1","Blood","16p12.1 ","16:21854731-22343312",488582,"Loss ","EEF2K, PDZD9, CDR2, POLR3E, C16orf52, UQCRC2, VWA3A, RRN3P3","Paternal","qPCR, Agilent 1M","present in 1 brother with autism","Uncertain (likely risk factor)","Rare recurrent 16p12.1 microdeletion (see above)","Autism on ADI-R and ADOS, low average IQ, language delay, some gross and fine motor coordination difficulties, no dysmorphic features or associated medical or psychiatric problems, no epilepsy. This case also carries a de novo 3p24.3 deletion. Brother also has the 16p12.1 microdeletion: autism on ADI-R and ADOS, low average IQ, language delay, some mild dysmorphic facial features, no epilepsy","Evidence of broader autism phenotype (social and communication domains) in both parents, with father scoring higher"]
["9809_202","M","Sporadic","Other","Stage 2","Blood","16p12.1 ","16:21854731:22351124",496394,"Loss ","EEF2K, CDR2, C16orf52, POLR3E, RRN3P3, UQCRC2, PDZD9, VWA3A","Unknown (not maternal)","(no validation attempted)","(not tested)","Uncertain (likely risk factor)","Rare recurrent 16p12.1 microdeletion (see above)","Autism (based on ADI-R and ADOS), no language delay, verbal, mild ID (WPPSI-III: VIQ 67, PIQ 65, FSIQ 66), seizures","N/A"]
["5134_3","F","Familial","Other","Stage 1","CL","16p12.1 ","16:21854731-22369458",514728,"Loss ","EEF2K, CDR2, C16orf52, POLR3E, RRN3P3, LOC641298, UQCRC2, PDZD9, VWA3A","Unknown (not paternal)","(no validation attempted)","(not tested)","Uncertain (likely risk factor)","Rare recurrent 16p12.1 microdeletion (see above)","Autism (based on ADI-R and ADOS), language delay (first words and phrases 60 mo), verbal, mild ID (Leiter PIQ 63)","N/A"]
["14335_4490","M","Sporadic","European","Stage 2","CL","16p12.1 ","16:21858916:22332295",473380,"Loss ","EEF2K, CDR2, RRN3P3, POLR3E, C16orf52, UQCRC2, PDZD9, VWA3A","Maternal","(no validation attempted)","(not tested)","Uncertain (likely risk factor)","Rare recurrent 16p12.1 microdeletion (see above)","Autism (based on ADI-R and ADOS), language delay, no functional language, average non-verbal development (Griffiths: language DQ 36, performance DQ 98, global DQ 67), no epilepsy","N/A"]
["4436_1","M","Sporadic","European","Stage 2","Blood","16p11.2","16:28721599-28957155",235557,"Loss","ATP2A1, ATXN2L, CD19, LAT, NFATC2IP, RABEP2, SH2B1, SPNS1, TUFM","Maternal","no validation attempted","(not tested)","Uncertain-likely pathogenic","Distal 16p11.2 deletion involving SH2B1. Recurrent microdeletion, associated with obesity, ID and schizophrenia, with incomplete penetrance and variable expressivity; further studies are needed to clarify their contribution to ASD (see Distal 16p11.2 region including SH2B1 in Highlighted genes in the Supplement)","ASD (ADI-R autism, ADOS not autism or ASD), no language delay (first words and phrases 15 mo), verbal, WISC-IV at 8 y 8 mo: VIQ 95, PIQ 67, FSIQ 76","N/A"]
["5382_3","M","Sporadic","European","Stage 1","Blood","16p11.2","16:28730274-28950951",220678,"Gain","ATP2A1, ATXN2L, CD19, LAT, NFATC2IP, RABEP2, SH2B1, SPNS1, TUFM","Maternal","qPCR","CNV also present in unaffected sib","Uncertain","Distal 16p11.2 duplication involving SH2B1. Recurrent reciprocal microdeletions are associated with obesity, ID and schizophrenia, with incomplete penetrance and variable expressivity; duplications have not been found to be consistently enriched in cases and further studies are needed to clarify their role as risk factors (see Distal 16p11.2 region including SH2B1 in Highlighted genes in the Supplement)","Autism (ADI-R and ADOS positive), language delay (first words 42 mo, first phrases 48 mo), verbal; IQ at 11 y 10 m: PPVT-IV VIQ 82, Leiter-R Brief PIQ 97","N/A"]
["3099_8","M","Familial","European","Stage 1","CL","16q21","16:60027157-61668976",1641820,"Loss","CDH8","Maternal","LR-PCR, Affy 10K","present in 2 other affected brothers but not in 4 unaffected siblings","Uncertain","CDH8 deletion (sequencing coordinates: chr16: 60025584–61667839, size: 1,642,256 bp) ","All 3 affected siblings have ASD and ID (for more details about this family see Pagnamenta et al. 2011b)","Mother unaffected"]
["2271_1","M","Sporadic","European","Stage 2","Blood","17p12","17:14040467-15435991",1395525,"Loss","CDRT1, CDRT15, CDRT4, CDRT7, COX10, FAM18B2, FAM18B2-CDRT4, HS3ST3B1, MGC12916, PMP22, TEKT3","Maternal","qPCR","(no siblings)","Uncertain (with respect to ID/ASD)","1.4 Mb deletion in 17p12 region (11 genes), including PMP22. PMP22 deletions cause hereditary neuropathy with liability to pressure palsies, while duplications cause Charcot-Marie-Tooth 1A. This CNV is clinically significant with respect to the peripheral neuropathy but considered of uncertain significance with respect to ID/ASD. Although mainly expressed in the peripheral nervous system, PMP22 is also expressed in the brain; a recent study reported decrease in white matter volume and cognitive impairment in 70% of cases with PMP22-associated disorders (Chanson et al. 2013). Further studies are needed to determine the contribution of PMP22 to ID/ASD.","PDD-NOS (autism on ADI-R, ASD on ADOS), language delay, normal IQ (WASI at 118 mo: VIQ 123, NVIQ 138, FSIQ 135), developmental coordination disorder, anxiety disorder, sleep disturbance, asthma, myopia, astigmatism","Both parents have OCD"]
["5056_4","M","Familial","European","Stage 1","Blood","17q12","17:34612208-34732327",120120,"Gain","FBXL20, RPL19, STAC2","De novo","qPCR, Illumina 1M for sibs","1 brother with autism (5056_3), no CNV; 3 other non-ASD brothers: 5056_5, CNV (could be mosaic); 5056_6, CNV; 5056_7, no CNV","Uncertain","Rare de novo duplication of 3 genes","Autism (based on ADI-R and ADOS), severe ID, below average language (<1%ile), no dysmorphic features, normal neurological exam, no epilepsy","N/A"]
["8463_202","M","Familial","European","Stage 2","Blood","17q22","17:52774693-52895975",121283,"Loss","MSI2","De novo","qPCR","no CNV in sib with PDD","Uncertain","Rare de novo intragenic deletion of MSI2","Autism (ADI-R and ADOS positive), no language delay (first words 15 mo, first phrases 18 mo), verbal, WISC-III at 8 y 7 mo: VIQ 97, PIQ 78, FSIQ 86","N/A"]
["5444_3","M","Sporadic","European","Stage 1","Blood","17q25.3","17:77785939-77849717",63779,"Loss","CSNK1D, SLC16A3","De novo","qPCR, Agilent 1M","1 non-ASD sister, no CNV","Uncertain","Rare de novo deletion of SLC16A3 and CSNK1D","Autism (based on ADI-R and ADOS), regression of language and motor skills at age 3 y, ID (unable to complete IQ measure), below average language (1%ile), myoclonic epilepsy, self-injurious behavior, sleep disorder (altered circadian rhythm according to parents), no dysmorphic features","Both parents are very social"]
["3477_3","M","Sporadic","European","Stage 2","Blood","18q12.1","18:30280260-30327512",47253,"Loss","DTNA","De novo","qPCR","absent in unaffected brother","Uncertain","Rare de novo DTNA deletion affecting only the first non-coding exon of the 4 longer isoforms. DTNA (dystrobrevin alpha) binds dystrophin, syntrophin, and proteins of dystrophin-associated glycoprotein complex, which is expressed in the brain and is involved in synaptic plasticity (see Highlighted genes in the Supplement)","ASD (ASD on ADI-R, autism on ADOS), verbal, low average IQ (WISC-R at 5 y 7 mo: VIQ 88, PIQ 88, FSIQ 86); no cardiac defects; no neuromuscular deficits","N/A"]
["14331_4450","M","Sporadic","European","Stage 2","Blood","18q23","18:72085223-73670156",1584934,"Loss","GALR1, LOC284276, MBP, ZNF236, ZNF516","De novo","qPCR","(2 healthy brothers, not tested)","Uncertain-likely pathogenic","1.6 Mb de novo deletion in 18q23 region encompassing 5 genes, including GALR1 (galanin receptor 1) and MBP (myelin basic protein gene), unique. This deletion overlaps the critical region of the 18q deletion syndrome for delayed brain myelination and growth hormone deficit (Cody et al. 2009)","Autism on ADI-R and ADOS, language delay, verbal, low normal IQ (Griffiths at 5 y 9 mo: language DQ 84, performance DQ 81, global DQ 82), no dysmorphic features except for slight epicanthus, no other anomalies, normal neurological exam, normal growth, no epilepsy, high plasma lactate. Negative family history. No phenotypic overlap with 18q deletion syndrome.","Both parents unaffected"]
["6358_6","M","Sporadic","European","Stage 1","Unknown (blood or CL)","19p13.3","19:4548413-5287389",738977,"Loss","ARRDC5, C19orf10, DPP9, FEM1A, KDM4B, MIR7-3, NCRNA00306, PLIN3, PTPRS, TICAM1, TNFAIP8L1, UHRF1","De novo","qPCR","(3 healthy sibs, no DNA)","Uncertain-likely pathogenic","739 kb de novo 19p13.3 deletion (12 genes); no similar deletions reported. PTPRS (protein tyrosine phosphatase receptor S) is involved in cell-cell interaction, axonogenesis and axon guidance.","Autism, language delay, low normal IQ, cleft palate, retrognathia, short philtrum, hypotelorism, strabismus, sandal gap, normal neurological exam, no epilepsy, normal brain MRI","Both parents healthy"]
["5046_3","M","Familial","Other","Stage 1","CL","20p12.3","20:8607242-8637441",30200,"Loss","PLCB1","De novo","qPCR","1 brother with ASD, no CNV","Uncertain","Rare de novo intragenic deletion of PLCB1","Autism (based on ADI-R and ADOS), unable to complete IQ measure, below average language (1%ile), no dysmorphic features, no epilepsy","N/A"]
["5335_3","M","Sporadic","European","Stage 1","CL","20p12.1","20:14545734-14948785",403052,"Loss","MACROD2, MACROD2-AS1","De novo","qPCR, Agilent 1M","(1 healthy sib, not tested)","Uncertain","Rare de novo partial deletion of MACROD2 and MACROD2-AS1","Autism (based on ADI-R and ADOS), moderate ID (Leiter NVIQ 36)","N/A"]
["20180_1704001","M","Sporadic","European","Stage 2","Blood","21q22.3","21:43018846-43444308",425463,"Gain","CBS, NDUFV3, PDE9A, PKNOX1, U2AF1, WDR4","De novo","qPCR","(not tested)","Uncertain","Rare de novo duplication of 425 kb (6 genes)","Autism (ADI-R and ADOS positive), no language delay (first words 10 mo, first phrases 14 mo), verbal, WAIS-III at 24 y: VIQ 122, PIQ 133, FSIQ 131; seizures","N/A"]
["8630_201","M","Familial (cousin has ASD)","European","Stage 2","Blood","22q12.3","22:32346124-32413987",67864,"Loss","LARGE","De novo","qPCR","(no siblings)","Uncertain","Rare de novo intragenic deletion of LARGE","Autism (ADI-R and ADOS positive), language delay (first phrases 48 mo), WASI at 13 y: VIQ 80, PIQ 101, FSIQ 89","N/A"]
["2175_1","M","Sporadic","European","Stage 2","Blood","22q13.2-qter","22:39729380-49582267",9852888,"(Uniparental disomy)","A4GALT, ACO2, ACR, ADM2, ALG12, ARFGAP3, ARHGAP8, ARSA, ATP5L2, ATXN10, BIK, BK250D10.8, BRD1, C22orf26, C22orf32, C22orf34, C22orf40, C22orf41, C22orf46, CCDC134, CELSR1, CENPM, CERK, CHADL, CHKB, CHKB-CPT1B, CN5H6.4, CPT1B, CRELD2, CSDC2, CYB5R3, CYP2D6, CYP2D7P1, EFCAB6, EP300, FAM109B, FAM116B, FAM118A, FAM19A5, FBLN1, FLJ46257, GRAMD4, GTSE1, HDAC10, IL17REL, KIAA0930, KIAA1644, KLHDC7B, L3MBTL2, LDOC1L, LMF2, LOC100132273, LOC100144603, LOC100271722, LOC150381, LOC388906, LOC730668, LOC90834, MAPK11, MAPK12, MAPK8IP2, MCAT, MEI1, MIOX, MIR1249, MIR1281, MIR3201, MIR33A, MIR3619, MIRLET7A3, MIRLET7B, MIRLET7BHG, MLC1, MOV10L1, MPPED1, NAGA, NCAPH2, NCRNA00207, NDUFA6, NFAM1, NHP2L1, NUP50, ODF3B, PACSIN2, PANX2, PARVB, PARVG, PHF21B, PHF5A, PIM3, PKDREJ, PLXNB2, PMM1, PNPLA3, PNPLA5, POLDIP3, POLR3H, PPARA, PPP6R2, PPPDE2, PRR5, PRR5-ARHGAP8, RABL2B, RANGAP1, RIBC2, RNU12, RPL23AP82, RRP7A, RRP7B, SAMM50, SBF1, SCO2, SCUBE1, SELO, SEPT3, SERHL, SERHL2, SHANK3, SHISA8, SMC1B, SREBF2, SULT4A1, TBC1D22A, TCF20, TEF, TNFRSF13C, TOB2, TRABD, TRMU, TSPO, TTC38, TTLL1, TTLL12, TUBGCP6, TYMP, UPK3A, WBP2NL, WNT7B, XRCC6, ZBED4, ZC3H7B","De novo","by exclusion (normal MLPA)","(1 unaffected sibling, no DNA)","Uncertain-likely benign","Mosaic segmental uniparental disomy (UPD) 22q13.2 to 22qter, 10 Mb, in approximately 24% of cells (blood DNA); normal 46,XY karyotype. The SNP array was initially interpreted as a mosaic gain, but normal MLPA and analysis of the level of mosaicism, using a formula based on the \"Bdev\" (deviation of the B allele frequency distribution) showed a UPD (Rodriguez-Santiago et al. 2011). Usually UPDs are pathogenic when they involve an imprinted locus or unmask a recessive mutation; there are no known imprinted loci in chr 22 and the recessive ID genes in the region would result in a severe phenotype not compatible with that observed in this case. A 25-year-old healthy male was reported with maternal UPD of the entire chr 22 (Schinzel et al. 1994)","Autism (meets ADI-R and ADOS criteria), language limited to a few words, self-injurious behavior, no dysmorphic features, head circumference 2.4 SD, no epilepsy","Both parents unaffected"]
["4316_1","F","Sporadic","European","Stage 2","Blood","entire chr X","X:1-154913754",154913754,"Gain","entire chromosome X","De novo","no validation attempted","(not tested)","Uncertain","Triple X syndrome. This is a relatively frequent cytogenetic abnormality, affecting 1/1000 females; psychiatric disorders appear to be more common in triple X syndrome and there have been a few case reports with ASD (chromosome abnormality)","ASD (based on medical history), verbal with history of speech/language delays, no ID (Kaufman Assessment Battery for Children, Mental Processing Composite score 87; WISC-III FSIQ 93), OCD, trichotillomania, history of attention deficit disorder, multiple sinusitis and pneumonia (3x) before age 5; no dysmorphic features","Mother depression; father Proteus syndrome, macrocephaly, hypotension, hypoglycemia, amblyopia"]
["4240_1","M","Sporadic","European","Stage 2","Blood","Xp22.31","X:6459601-8095053",1635453,"Loss","HDHD1, MIR651, PNPLA4, STS, VCX, VCX3A","Maternal (X-linked in a male)","qPCR","present in unaffected sister (X-linked)","Uncertain","1.6 Mb Xp22.31 deletion (6 genes, including STS). STS deletions or mutations cause X-linked ichthyosis, present in the subject (reported in Griswold et al. 2012a). This is a recurrent deletion, due to complex rearrangements between similar sequences of homologous genes in the region, the VCX gene family. Deletions in this region are associated with neurological phenotypes (ID, ASD, ADHD) but the causal gene(s) has not yet been identified. VCX-A haploinsufficiency has been postulated to be responsible for the ID phenotype but there is no clear evidence of its contribution.","Autism based on medical history, ASD based on ADI-R (missed criteria by one point on repetitive domain); language delay - phrase speech, language disorder; ID (Bayley Scale of Infant Development at 33 mo: Mental Developmental Index 21; Vineland Adaptive Behavior Composite score 45 at 9 y); ichthyosis vulgaris, no dysmorphic features (reported in Griswold et al. 2012a, family 7955)","Mother anxiety disorder, ADHD, bipolar disorder, migraines; father thyroid cancer"]
["9900_203","M","Sporadic","Other ","Stage 2","Blood","Xp22.12","X:19396116-19509785",113670,"Gain","MAP3K15, SH3KBP1","Maternal (X-linked in a male)","qPCR","(not tested)","Uncertain","Rare partial duplication of SH3KBP1 and MAP3K15, maternal (X-linked). No increased SH3KBP1 expression was observed in cell lines, suggesting that this partial duplication is unlikely to be deleterious. SH3KBP1 is a candidate gene (see Highlighted genes in the Supplement)","Autism (meets criteria on ADI-R and ADOS), language delay (first words 18 mo, first phrases 42 mo), limited language, moderate ID (Bayley Scales of Infant Development II, mental developmental index 45), strabismus (like his mother), normal physical exam, no dysmorphic features, no epilepsy","Mother unaffected"]
["17031_1","M","Sporadic","European","Stage 2","Blood","Xp22.12","X:19450969-19845766",394798,"Loss","CXorf23, SH3KBP1","Maternal (X-linked in a male)","qPCR","(not tested)","Uncertain","Rare deletion involving SH3KBP1 and CXorf23, maternal (X-linked). SH3KBP1 is a candidate gene (see Highlighted genes in the Supplement)","Autism (based on ADI-R and ADOS), language delay, verbal, VIQ 79; Vineland: Communication 21, Daily Living Skills 47, Socialization 38, Adaptive Behavior Composite 32; physical examination at 5 y 8 mo revealed no dysmorphic features, neurological examination was normal except for a deficit in coordination and gross and fine motor development; no seizures, normal sleep EEG. Negative family history of neuropsychiatric disorders","Mother unaffected"]
["5521_3","M","Sporadic","European","Stage 1","Blood","Xp22.12","X:19471138-19861338",390201,"Gain","CXorf23, SH3KBP1","Maternal","qPCR","2 non-ASD sisters, no CNV in either","Uncertain","Rare partial duplication of SH3KBP1 and CXorf23, maternal (X-linked). SH3KBP1 is a candidate gene (see Highlighted genes in the Supplement)","Autism (based on ADI-R and ADOS), below average IQ (<1%ile), nonverbal, seizure disorder, coarse facial features","Mother unaffected"]
["16076_1571045001","M","Sporadic","European","Stage 2","CL","Xp22.11","X:22768481-23133948",365468,"Loss","DDX53 (upstream of PTCHD1)","De novo","qPCR","(1 unaffected sibling, not tested)","Uncertain","DDX53 deletion, upstream of PTCHD1 in a male, de novo","Autism (autism on ADI-R and ADOS), language delay (first words 21 mo, first phrases 60 mo), verbal, borderline IQ (WISC-III at 36 y: VIQ 68, PIQ 82, FSIQ 73), normal physical exam, no seizure history","Father unaffected, mother OCD and depression"]
["13047_563","M","Familial","European","Stage 1","Blood","Xp22.11","X:22829183-23214712",385530,"Loss","DDX53 (upstream of PTCHD1)","Maternal (X-linked in a male)","qPCR","2 affected brothers, one with autism and the other with ASD, no deletion (1 sister with pragmatic language disorder, no DNA)","Uncertain","Deletion upstream of PTCHD1, maternally inherited in a male","Autism (based on ADI-R and ADOS), history of language delay followed by rapid language learning progression, normal IQ, no dysmorphic features, history of allergies and recurrent ear infections, no epilepsy (reported in Noor et al. 2010)","Mother unaffected"]
["5111_3","M","Familial","European","Stage 1","Blood","Xp22.11","X:22844170-22897714",53545,"Loss","— (upstream of PTCHD1)","Maternal (X-linked in a male)","qPCR, Illumina 1M-duo for sibs","1 brother with autism, no CNV; present in 1 non-ASD sister","Uncertain","Deletion upstream of PTCHD1, maternally inherited in a male","Autism (based on ADI-R and ADOS), language delay, non-verbal at age 8, below average IQ (Leiter NVIQ 46), no epilepsy; physical examination normal except for some mild dysmorphic facial features and a large head circumference; normal brain MRI (reported in Noor et al. 2010)","Mother unaffected, some academic difficulties noted"]
["3253_4","M","Familial","European","Stage 1","Buccal","Xp22.11","X:22860224-22907454",47231,"Loss","— (upstream of PTCHD1)","Maternal (X-linked in a male)","qPCR","absent in 1 brother with autism and 1 unaffected younger sister ","Uncertain","Deletion upstream of PTCHD1, maternally inherited in a male","Autism (based on ADI-R and ADOS), mild ID (VIQ=56, NVIQ=75) (reported in Noor et al. 2010)","Mother unaffected"]
["5065_3","M","Familial","European","Stage 1","Blood","Xp22.11","X:22860224-22923580",63357,"Loss","— (upstream of PTCHD1)","Maternal (X-linked in a male)","qPCR","1 brother with autism, no CNV","Uncertain","Deletion upstream of PTCHD1, maternally inherited in a male","Autism (based on ADI-R and ADOS), language delay (first words 22 mo, first phrases 42 mo), verbally fluent, below average nonverbal IQ (Leiter PIQ 71), spina bifida oculta, high arched palate, no other dysmorphic features noted, no epilepsy (reported in Noor et al. 2010)\nBrother (no deletion): autism (based on ADI-R and ADOS), verbally fluent; Vineland: Communication 71, Daily Living Skills 38, Socialization 51, Adaptive Behavior Composite 49","Both parents unaffected"]
["5298_3","M","Sporadic (2nd degree cousin Asperger)","European","Stage 1","Blood","Xp22.11","X:22892380-23013494",121115,"Loss","DDX53 (upstream of\nPTCHD1)","Maternal (X-linked in a male)","qPCR, Agilent 1M and Illumina 1M-duo for sibs","present in 1 non-ASD sister (5298_4)","Uncertain","DDX53 deletion, upstream of PTCHD1, maternally inherited in a male","Autism (based on ADI-R and ADOS), moderate ID (Leiter Brief IQ 42, PPVT-4 20), Vineland: Communication <20, Daily Living Skills 47, Socialization 44, Adaptive Behavior Composite 34; severe language impairment, speech and oral motor deficit, uses single words; possible history of seizures; pes planus and genu varus bilaterally, no other dysmorphic features; normal brain CT scan (reported in Noor et al. 2010)","Mother unaffected"]
["3424_3","M","Sporadic","European","Stage 1","Blood","Xp22.11","X:23013250-23116188",102939,"Loss","— (upstream of PTCHD1)","Maternal (X-linked in a male)","qPCR","absent in 1 unaffected brother","Uncertain","Deletion upstream of PTCHD1, maternally inherited in a male","Autism (based on ADI-R and ADOS), mild ID (WISC-R: VIQ 50, NVIQ 58, FSIQ 50), relative macrocephaly, no dysmorphic features (reported in Noor et al. 2010). This case also has an MBD5 partial duplication, maternal, of uncertain clinical significance ","Mother unaffected"]
["Abbreviations: ADHD, attention deficit hyperactivity disorder; ADI-R, Autism Diagnostic Interview-Revised; ADOS, Autism Diagnostic Observation Schedule; AGP, Autism Genome Project; ASD, autism spectrum disorder; BAPQ, Broad Autism Phenotype Questionnaire; BMI, body mass index; BP, breakpoint; CL, cell line (peripheral blood lymphoblastoid cell line); CT, computerized tomography; DECIPHER, Database of Chromosomal Imbalance and Phenotype in Humans using Ensembl Resources; DGV, Database of Genomic Variants; DQ, developmental quotient (Griffiths Developmental Scales); EEG, electroencephalography; F, female; FSIQ, full scale IQ; ID, intellectual disability; IQ, intellectual quotient; ISCA, International Standards for Cytogenomic Arrays database; LR-PCR, long range PCR; M, male; MLPA, multiplex ligation-dependent probe amplification; MRI, magnetic resonance imaging; N/A, not available; NVIQ, non verbal IQ; OCD, obsessive-compulsive disorder; OWLS, Oral and Written Language Scale; PDD-NOS, pervasive developmental disorder-not otherwise specified; PIQ, performance IQ; PPVT, Peabody Picture Vocabulary Test; qPCR, quantitative PCR; SD, standard deviation; SRS, Social Responsiveness Scale; SSRI, selective serotonin reuptake inhibitor; VIQ, verbal IQ; WAIS, Wechsler Adult Intelligence Scale; WASI, Wechsler Abbreviated Scale of Intelligence; WISC, Wechsler Intelligence Scale for Children; WPPSI, Wechsler Preschool and Primary Scale of Intelligence; XLID, X-linked intellectual disability"]

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["References"]
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