Supernumerary isodicentric chromosome 15 in Patient 1. A. Metaphase FISH of lymphoblastoid cell lines from Patient 1 using probes UBE3A (red) for the region of interest and D15S936 (green) as a control probe in 15q26.3 showed two normal signals on chromosomes 15 as well as additional hybridization spots of the duplicated 15q11-q13 region (red) on a supernumerary chromosome (arrow). B. Quantitative microsatellite analyses showed increased dosage of D15S11, D15S817 and D15S815 in the proband, but not in her parents. C. MPLA confirmed increased copy number of all the probes in the 15q11-q13 region between BP1 and BP4 (from TUBGCP5 to APBA2), and normal dosage of BLM and IGF1, located at the distal end of the chromosome, at 15q26. The peak heights above 1.5 are consistent with tetrasomy of the region. D. Genotyping of microsatellites in the 15q11-q13 region revealed three alleles for informative markers between BP1 and BP4, with one allele of paternal origin and two of maternal origin. The presence of one informative microsatellite, D15S1031, with a single maternal allele indicates that the breakpoint lies proximal to this marker. E. Genomic qPCR showed a transition from increased copy number to normal dosage between KLF13 and OTUD7A, indicating that the distal breakpoint lies between BP4 and BP5.