MATERNAL DISOMY AND PRADER-WILLI-SYNDROME CONSISTENT WITH GAMETE COMPLEMENTATION IN A CASE OF FAMILIAL TRANSLOCATION (3-15) (P25-Q11.2)

Maternal uniparental disomy (UPD) for chromosome 15 is responsible for an estimated 30% of cases of Prader-Willi syndrome (PWS). We report o n an unusual case of maternal disomy 15 in PWS that is most consistent with adjacent-1 segregation of a paternal t(3;15)(p25;q11.2) with sim ultaneous maternal meiotic nondisjunction for chromosome 15, The patie nt (J,B.), a 17-year-old white male with PWS, was found to have 47 chr omosomes with a supernumerary, paternal der(15) consisting of the shor t arm and the proximal long arm of chromosome 15, and distal chromosom e arm 3p, The t(3;15) was present in the balanced state in the patient 's father and a sister. Fluorescent in situ hybridization analysis dem onstrated that the PWS critical region resided on the derivative chrom osome 3 and that there was no deletion of the PWS region on the normal pair of 15s present in J.B, Methylation analysis at exon alpha of the small nuclear ribonucleoprotein-associated polypeptide N (SNRPN) gene showed a pattern characteristic of only the maternal chromosome 15 in J.B. Maternal disomy was confirmed by polymerase chain reaction analy sis of microsatellite repeats at the gamma-aminobutyric acid receptor beta3 subunit (GABRB3) locus. A niece (B.B.) with 45 chromosomes and t he derivative 3 but without the der(15) demonstrated a phenotype consi stent with that reported for haploinsufficiency of distal 3 p, Unipare ntal disomy associated with unbalanced segregation of non-Robertsonian translocations has been reported previously but has not, to our knowl edge, been observed in a case of PWS. Furthermore, our findings are be st interpreted as true gamete complementation resulting in maternal UP D 15 and PWS, Am. J, Med, Genet. 78:134-139, 1998, (C) 1998 Wiley-Liss , Inc.