. Department-of-genetics and . Ap-hp, 48 boulevard Sérurier, 75019 Paris, France. 2 INSERM, UMR 1130

. Quai-saint and I. Bernard, 7 Fondation Fondamental, 40 rue de Mesly, 94000 Créteil, France. 8 Gillberg Neuropsychiatry Centre Kungsgatan 12, 41119 Göteborg, Sweden. 9 Département de Génétique et Procréation, Neurology Unit, AP-HP Medical Genetics Unit Cytogenetics Unit Medical Genetics Unit, vol.47, issue.26 13, pp.15-29

9. Juillet and F. Bondy, 16 Foundation for Autism Research, 3081 Quail Hollow 17 Department of Psychiatry, AP-HP, Henri Mondor-Albert Chenevier Hospital, 40 rue de Mesly, 18 INSERM U955, Institut Mondor de Recherche Biomédicale, pp.94000-94010, 2014.

R. 1. Jacobs, P. Browne, C. Gregson, N. Joyce, C. White et al., Estimates of the frequency of chromosome abnormalities detectable in unselected newborns using moderate levels of banding., Journal of Medical Genetics, vol.29, issue.2, pp.103-111, 1992.
DOI : 10.1136/jmg.29.2.103

D. Warburton, De novo balanced chromosome rearrangements and extra marker chromosomes identified at prenatal diagnosis: clinical significance and distribution of breakpoints, Am J Hum Genet, vol.49, issue.5, pp.995-1013, 1991.

S. Gribble, E. Prigmore, D. Burford, K. Porter, B. Ng et al., The complex nature of constitutional de novo apparently balanced translocations in patients presenting with abnormal phenotypes, Journal of Medical Genetics, vol.42, issue.1, pp.8-16, 2005.
DOI : 10.1136/jmg.2004.024141

D. Gregori, M. Ciccone, R. Magini, P. Pramparo, T. Gimelli et al., Cryptic deletions are a common finding in "balanced" reciprocal and complex chromosome rearrangements: a study of 59 patients, Journal of Medical Genetics, vol.44, issue.12, pp.750-62, 2007.
DOI : 10.1136/jmg.2007.052787

A. Higgins, F. Alkuraya, A. Bosco, K. Brown, G. Bruns et al., Characterization of Apparently Balanced Chromosomal Rearrangements from the Developmental Genome Anatomy Project, The American Journal of Human Genetics, vol.82, issue.3, pp.712-734, 2008.
DOI : 10.1016/j.ajhg.2008.01.011

J. Baptista, C. Mercer, E. Prigmore, S. Gribble, N. Carter et al., Breakpoint Mapping and Array CGH in Translocations: Comparison of a Phenotypically Normal and an Abnormal Cohort, The American Journal of Human Genetics, vol.82, issue.4, pp.927-963, 2008.
DOI : 10.1016/j.ajhg.2008.02.012

C. Sismani, S. Kitsiou-tzeli, M. Ioannides, C. Christodoulou, V. Anastasiadou et al., Cryptic genomic imbalances in patients with de novo or familial apparently balanced translocations and abnormal phenotype, Molecular Cytogenetics, vol.1, issue.1, p.15, 2008.
DOI : 10.1186/1755-8166-1-15

C. Schluth-bolard, B. Delobel, D. Sanlaville, O. Boute, J. Cuisset et al., Cryptic genomic imbalances in de novo and inherited apparently balanced chromosomal rearrangements: Array CGH study of 47 unrelated cases, European Journal of Medical Genetics, vol.52, issue.5
DOI : 10.1016/j.ejmg.2009.05.011
URL : https://hal.archives-ouvertes.fr/inserm-00405484

A. Gijsbers, C. Bosch, J. Dauwerse, O. Giromus, K. Hansson et al., Additional cryptic CNVs in mentally retarded patients with apparently balanced karyotypes, European Journal of Medical Genetics, vol.53, issue.5, pp.227-260, 2010.
DOI : 10.1016/j.ejmg.2010.06.003

I. Feenstra, N. Hanemaaijer, B. Sikkema-raddatz, H. Yntema, T. Dijkhuizen et al., Balanced into array: genome-wide array analysis in 54 patients with an apparently balanced de novo chromosome rearrangement and a meta-analysis, European Journal of Human Genetics, vol.17, issue.11, pp.1152-60, 2011.
DOI : 10.1136/jmg.39.8.e41
URL : https://hal.archives-ouvertes.fr/hal-00655429

C. Betancur, Etiological heterogeneity in autism spectrum disorders: More than 100 genetic and genomic disorders and still counting, Brain Research, vol.1380, pp.42-77, 2011.
DOI : 10.1016/j.brainres.2010.11.078
URL : https://hal.archives-ouvertes.fr/inserm-00549873

J. Murdoch and M. State, Recent developments in the genetics of autism spectrum disorders, Current Opinion in Genetics & Development, vol.23, issue.3, pp.310-315, 2013.
DOI : 10.1016/j.gde.2013.02.003

M. Kielinen, H. Rantala, E. Timonen, S. Linna, and I. Moilanen, Associated Medical Disorders and Disabilities in Children with Autistic Disorder, Autism, vol.8, issue.1, pp.49-60, 2004.
DOI : 10.1177/1362361304040638

Y. Shen, K. Dies, I. Holm, C. Bridgemohan, M. Sobeih et al., Clinical Genetic Testing for Patients With Autism Spectrum Disorders, PEDIATRICS, vol.125, issue.4, pp.727-762, 2010.
DOI : 10.1542/peds.2009-1684

F. Devillard, V. Guinchat, D. Moreno-de-luca, A. Tabet, N. Gruchy et al., Paracentric inversion of chromosome 2 associated with cryptic duplication of 2q14 and deletion of 2q37 in a patient with autism, American Journal of Medical Genetics Part A, vol.4, issue.9, pp.2346-54, 2010.
DOI : 10.1002/ajmg.a.33601
URL : https://hal.archives-ouvertes.fr/inserm-00520816

C. Haldeman-englert, K. Chapman, H. Kruger, E. Geiger, D. Mcdonald-mcginn et al., A de novo 8.8-Mb deletion of 21q21.1-q21.3 in an autistic male with a complex rearrangement involving chromosomes 6, 10, and 21, American Journal of Medical Genetics Part A, vol.2, issue.1, pp.196-202, 2010.
DOI : 10.1002/ajmg.a.33176

C. Depienne, D. Moreno-de-luca, D. Heron, D. Bouteiller, A. Gennetier et al., Screening for Genomic Rearrangements and Methylation Abnormalities of the 15q11-q13 Region in Autism Spectrum Disorders, Biological Psychiatry, vol.66, issue.4, pp.349-59, 2009.
DOI : 10.1016/j.biopsych.2009.01.025
URL : https://hal.archives-ouvertes.fr/inserm-00369261

H. Kearney, E. Thorland, K. Brown, F. Quintero-rivera, and S. South, American College of Medical Genetics standards and guidelines for interpretation and reporting of postnatal constitutional copy number variants, Genetics in Medicine, vol.45, issue.7, pp.680-685, 2011.
DOI : 10.1097/GIM.0b013e3182217a3a

A. Tabet, A. Aboura, M. Gerard, M. Pilorge, C. Dupont et al., Molecular characterization of a de novo 6q24.2q25.3 duplication interrupting UTRN in a patient with arthrogryposis, American Journal of Medical Genetics Part A, vol.51, issue.7, pp.1781-1789, 2010.
DOI : 10.1002/ajmg.a.33433
URL : https://hal.archives-ouvertes.fr/inserm-00520796

M. Aldred, R. Sanford, N. Thomas, M. Barrow, L. Wilson et al., Molecular analysis of 20 patients with 2q37.3 monosomy: definition of minimum deletion intervals for key phenotypes, Journal of Medical Genetics, vol.41, issue.6, pp.433-442, 2004.
DOI : 10.1136/jmg.2003.017202

J. Buxbaum, G. Cai, P. Chaste, G. Nygren, J. Goldsmith et al., Mutation screening of the PTEN gene in patients with autism spectrum disorders and macrocephaly, Am J Med Genet B Neuropsychiatr Genet, vol.144, issue.4, pp.484-91, 2007.
URL : https://hal.archives-ouvertes.fr/inserm-00125293

G. De and C. Francais, Pericentric inversions in man. A French collaborative study, Ann Genet, vol.29, issue.3, pp.129-68, 1986.

L. Hsu, P. Benn, H. Tannenbaum, T. Perlis, and A. Carlson, Chromosomal polymorphisms of 1, 9, 16, and Y in 4 major ethnic groups: A large prenatal study, American Journal of Medical Genetics, vol.19, issue.1, pp.95-101, 1987.
DOI : 10.1002/ajmg.1320260116

N. Thomas, V. Bryant, V. Maloney, A. Cockwell, and P. Jacobs, Investigation of the origins of human autosomal inversions, Human Genetics, vol.49, issue.6, pp.607-623, 2008.
DOI : 10.1007/s00439-008-0510-z

G. Van-buggenhout, C. Melotte, B. Dutta, G. Froyen, P. Van-hummelen et al., Mild Wolf-Hirschhorn syndrome: micro-array CGH analysis of atypical 4p16.3 deletions enables refinement of the genotype-phenotype map, Journal of Medical Genetics, vol.41, issue.9, pp.691-699, 2004.
DOI : 10.1136/jmg.2003.016865

J. Ravnan, J. Tepperberg, P. Papenhausen, A. Lamb, J. Hedrick et al., Subtelomere FISH analysis of 11 688 cases: an evaluation of the frequency and pattern of subtelomere rearrangements in individuals with developmental disabilities, Journal of Medical Genetics, vol.43, issue.6, pp.478-89, 2006.
DOI : 10.1136/jmg.2005.036350

S. Patel, H. Dagnew, A. Parekh, E. Koenig, R. Conte et al., Clinical manifestations of trisomy 4p syndrome, European Journal of Pediatrics, vol.92, issue.Suppl, pp.425-456, 1995.
DOI : 10.1007/BF02029349

P. Cotter, S. Kaffe, L. Li, I. Gershin, and K. Hirschhorn, Loss of subtelomeric sequence associated with a terminal inversion duplication of the short arm of chromosome 4, American Journal of Medical Genetics, vol.82, issue.1, pp.76-80, 2001.
DOI : 10.1002/1096-8628(20010722)102:1<76::AID-AJMG1389>3.0.CO;2-4

M. Gerard-blanluet, R. S. Munier, C. , L. Lorc-'h, M. Kanafani et al., Classical West ???syndrome??? phenotype with a subtelomeric 4p trisomy, American Journal of Medical Genetics Part A, vol.1, issue.3, pp.299-302, 2004.
DOI : 10.1002/ajmg.a.30314

M. Roselló, S. Monfort, C. Orellana, I. Ferrer-bolufer, R. Quiroga et al., Submicroscopic duplication of the Wolf-Hirschhorn critical region with a 4p terminal deletion, Cytogenet Genome Res, vol.125, issue.2, pp.103-111, 2009.

E. Carmany and E. Bawle, Microduplication of 4p16.3 due to an unbalanced translocation resulting in a mild phenotype, American Journal of Medical Genetics Part A, vol.148, issue.4, pp.819-843, 2011.
DOI : 10.1002/ajmg.a.33916

L. Wu, D. Meng, Z. Zhou, J. Du, Z. Long et al., A family with partial duplication/deletion 4p due to a balanced t (4; 15) (p16.2; p11.2) translocation, American Journal of Medical Genetics Part A, vol.148, issue.3, pp.656-665, 2011.
DOI : 10.1002/ajmg.a.33867

B. Schonewolf-greulich, K. Ravn, B. Hamborg-petersen, K. Brondum-nielsen, and Z. Tumer, Segregation of a 4p16.3 duplication with a characteristic appearance, macrocephaly, speech delay and mild intellectual disability in a 3-generation family, American Journal of Medical Genetics Part A, vol.79, issue.9, pp.2358-62, 2013.
DOI : 10.1002/ajmg.a.36099

F. Hannes, M. Drozniewska, J. Vermeesch, and O. Haus, Duplication of the Wolf-Hirschhorn syndrome critical region causes neurodevelopmental delay, European Journal of Medical Genetics, vol.53, issue.3
DOI : 10.1016/j.ejmg.2010.02.004

A. Cyr, M. Nimmakayalu, S. Longmuir, S. Patil, K. Keppler-noreuil et al., A novel 4p16.3 microduplication distal to WHSC1 and WHSC2 characterized by oligonucleotide array with new phenotypic features, American Journal of Medical Genetics Part A, vol.98, issue.9, pp.2224-2232, 2011.
DOI : 10.1002/ajmg.a.34120

D. Pinto, E. Delaby, D. Merico, M. Barbosa, A. Merikangas et al., Convergence of Genes and Cellular Pathways Dysregulated in Autism Spectrum Disorders, The American Journal of Human Genetics, vol.94, issue.5, pp.677-94, 2014.
DOI : 10.1016/j.ajhg.2014.03.018
URL : https://hal.archives-ouvertes.fr/inserm-00986225

M. Sogaard, Z. Tumer, H. Hjalgrim, J. Hahnemann, B. Friis et al., Subtelomeric study of 132 patients with mental retardation reveals 9 chromosomal anomalies and contributes to the delineation of submicroscopic deletions of 1pter, BMC Med Genet, vol.26, pp.4-5, 2005.

G. Fisch, P. Grossfeld, R. Falk, A. Battaglia, J. Youngblom et al., Cognitive-behavioral features of Wolf-Hirschhorn syndrome and other subtelomeric microdeletions, American Journal of Medical Genetics Part C: Seminars in Medical Genetics, vol.148, issue.4, pp.417-443, 2010.
DOI : 10.1002/ajmg.c.30279

Y. Kondoh, T. Toma, H. Ohashi, N. Harada, K. Yoshiura et al., Inv dup del(4)(:p14 ? p16.3::p16.3 ? qter) with manifestations of partial duplication 4p and Wolf-Hirschhorn syndrome, American Journal of Medical Genetics, vol.94, issue.1, pp.123-129, 2003.
DOI : 10.1002/ajmg.a.20208

G. Paskulin, M. Riegel, P. Cotter, A. Kiss, R. Rosa et al., Inv dup del(4)(:p13?????????p16.3::p16.3?????????qter) in a girl without typical manifestations of Wolf-Hirschhorn syndrome, American Journal of Medical Genetics Part A, vol.72, issue.6, pp.1302-1309, 2009.
DOI : 10.1002/ajmg.a.32888

M. Beaujard, J. Jouannic, B. Bessieres, C. Borie, I. Martin-luis et al., Prenatal detection of ade novo terminal inverted duplication 4p in a fetus with the Wolf-Hirschhorn syndrome phenotype, Prenatal Diagnosis, vol.82, issue.6, pp.451-456, 2005.
DOI : 10.1002/pd.1154

O. Zuffardi, M. Bonaglia, R. Ciccone, and R. Giorda, Inverted duplications deletions: underdiagnosed rearrangements??, Clinical Genetics, vol.9, issue.(1), pp.505-518, 2009.
DOI : 10.1111/j.1399-0004.2009.01187.x

L. Rowe, J. Lee, L. Rector, E. Kaminsky, A. Brothman et al., U-type exchange is the most frequent mechanism for inverted duplication with terminal deletion rearrangements, Journal of Medical Genetics, vol.46, issue.10, pp.694-702, 2009.
DOI : 10.1136/jmg.2008.065052

S. Yu and W. Graf, Telomere Capture as a Frequent Mechanism for Stabilization of the Terminal Chromosomal Deletion Associated with Inverted Duplication, Cytogenetic and Genome Research, vol.129, issue.4, pp.265-74, 2010.
DOI : 10.1159/000315887

U. Wester, M. Bondeson, C. Edeby, and G. Anneren, Clinical and molecular characterization of individuals with 18p deletion: A genotype???phenotype correlation, American Journal of Medical Genetics Part A, vol.39, issue.11, pp.1164-71, 2006.
DOI : 10.1002/ajmg.a.31260

J. Hoy, J. Constable, S. Vicini, Z. Fu, and P. Washbourne, SynCAM1 recruits NMDA receptors via Protein 4.1B, Molecular and Cellular Neuroscience, vol.42, issue.4, pp.466-83, 2009.
DOI : 10.1016/j.mcn.2009.09.010

C. Leroy, E. Landais, S. Briault, A. David, O. Tassy et al., The 2q37-deletion syndrome: an update of the clinical spectrum including overweight, brachydactyly and behavioural features in 14 new patients, European Journal of Human Genetics, vol.16, issue.6, pp.602-614, 2013.
DOI : 10.1016/j.anngen.2004.03.002

S. Williams, M. Aldred, D. Kaloustian, V. Halal, F. Gowans et al., Haploinsufficiency of HDAC4 Causes Brachydactyly Mental Retardation Syndrome, with Brachydactyly Type E, Developmental Delays, and Behavioral Problems, The American Journal of Human Genetics, vol.87, issue.2, pp.219-247, 2010.
DOI : 10.1016/j.ajhg.2010.07.011

H. Cukier, D. Skaar, M. Rayner-evans, I. Konidari, P. Whitehead et al., Identification of chromosome 7 inversion breakpoints in an autistic family narrows candidate region for autism susceptibility, Autism Research, vol.140, issue.5, pp.258-66, 2009.
DOI : 10.1002/aur.96

J. Vincent, S. Choufani, S. Horike, B. Stachowiak, M. Li et al., A translocation t(6;7)(p11???p12;q22) associated with autism and mental retardation: localization and identification of candidate genes at the breakpoints, Psychiatric Genetics, vol.18, issue.3, pp.101-110, 2008.
DOI : 10.1097/YPG.0b013e3282f97df7

T. Walsh, J. Mcclellan, S. Mccarthy, A. Addington, S. Pierce et al., Rare Structural Variants Disrupt Multiple Genes in Neurodevelopmental Pathways in Schizophrenia, Science, vol.320, issue.5875, pp.539-582, 2008.
DOI : 10.1126/science.1155174

T. Sahoo, A. Theisen, J. Rosenfeld, A. Lamb, J. Ravnan et al., Copy number variants of schizophrenia susceptibility loci are associated with a spectrum of speech and developmental delays and behavior problems, Genetics in Medicine, vol.22, issue.10, pp.868-80, 2011.
DOI : 10.1097/GIM.0b013e3182217a06

X. Hauge, G. Raca, S. Cooper, K. May, R. Spiro et al., Detailed characterization of, and clinical correlations in, 10 patients with distal deletions of chromosome 9p, Genetics in Medicine, vol.91, issue.8, pp.599-611, 2008.
DOI : 10.1097/GIM.0b013e31817e2bde

E. Bonnafe, M. Touka, A. Aitlounis, D. Baas, E. Barras et al., The Transcription Factor RFX3 Directs Nodal Cilium Development and Left-Right Asymmetry Specification, Molecular and Cellular Biology, vol.24, issue.10, pp.4417-4444, 2004.
DOI : 10.1128/MCB.24.10.4417-4427.2004
URL : https://hal.archives-ouvertes.fr/hal-00145023

D. Baas, A. Meiniel, C. Benadiba, E. Bonnafe, O. Meiniel et al., A deficiency in RFX3 causes hydrocephalus associated with abnormal differentiation of ependymal cells, European Journal of Neuroscience, vol.18, issue.4, pp.1020-1050, 2006.
DOI : 10.1111/j.1460-9568.2006.05002.x
URL : https://hal.archives-ouvertes.fr/hal-00192833

C. Benadiba, D. Magnani, M. Niquille, L. Morle, D. Valloton et al., The Ciliogenic Transcription Factor RFX3 Regulates Early Midline Distribution of Guidepost Neurons Required for Corpus Callosum Development, PLoS Genetics, vol.30, issue.3, p.1002606, 2012.
DOI : 10.1371/journal.pgen.1002606.s007
URL : https://hal.archives-ouvertes.fr/hal-00720081

M. Talkowski, J. Rosenfeld, I. Blumenthal, V. Pillalamarri, C. Chiang et al., Sequencing Chromosomal Abnormalities Reveals Neurodevelopmental Loci that Confer Risk across Diagnostic Boundaries, Cell, vol.149, issue.3, pp.525-562, 2012.
DOI : 10.1016/j.cell.2012.03.028
URL : http://doi.org/10.1016/j.cell.2012.03.028

C. Schluth-bolard, A. Labalme, M. Cordier, M. Till, G. Nadeau et al., Breakpoint mapping by next generation sequencing reveals causative gene disruption in patients carrying apparently balanced chromosome rearrangements with intellectual deficiency and/or congenital malformations, Journal of Medical Genetics, vol.50, issue.3, pp.144-50, 2013.
DOI : 10.1136/jmedgenet-2012-101351

P. Bitoun, C. Philippe, M. Cherif, M. Mulcahy, and S. Gilgenkrantz, Incontinentia pigmenti (type 1) and X;5 translocation, Ann Genet, vol.35, issue.1, pp.51-55, 1992.