BLOOM-SYNDROME AND MATERNAL UNIPARENTAL DISOMY FOR CHROMOSOME-15

Bloom syndrome (BS) is an autosomal recessive disorder characterized b y increases in the frequency of sister-chromatid exchange and in the i ncidence of malignancy. Chromosome-transfer studies have shown the BS locus to map to chromosome 15q. This report describes a subject with f eatures of both BS and Prader-Willi syndrome (PWS). Molecular analysis showed maternal uniparental disomy for chromosome 15. Meiotic recombi nation between the two disomic chromosomes 15 has resulted in heterodi somy for proximal 15q and isodisomy for distal 15q. In this individual BS is probably due to homozygosity for a gene that is telomeric to D1 5S95 (15q25), rather than to genetic imprinting, the mechanism respons ible for the development of PWS. This report represents the first appl ication of disomy analysis to the regional localization of a disease g ene. This strategy promises to be useful in the genetic mapping of oth er uncommon autosomal recessive conditions.