PRADER-WILLI-SYNDROME IN A CHILD WITH MOSAIC TRISOMY-15 AND MOSAIC TRIPLO-X - A MOLECULAR ANALYSIS

A 3.3 year old girl with Prader-Willi syndrome (PWS) and mosaicism for two aneuploidies, 47,XXX and 47,XX,+15, is presented. The triplo-X ce ll Line was found in white blood cells and fibroblasts, the trisomy 15 cell line in 50% of the fibroblasts. Using methylation studies of the PWS critical region and by polymorphic microsatellite analysis, the e xistence of uniparental maternal heterodisomy for chromosome 15 was sh own in white blood cells. This provided a molecular explanation for th e PWS in this child. In fibroblasts, an additional paternal allele was detected for markers on chromosome 15, which is in agreement with the presence of mosaicism for trisomy 15 in these cells. This example pro vides direct evidence for trisomic rescue by reduction to disomy as a possible basis for PWS. Whereas the trisomy 15 was caused by a materna l meiosis I error, the triplo-X resulted from a postzygotic gain of a maternal X chromosome, as shown by the finding of two identical matern al X chromosomes in the 47,XXX cell line. Because the triplo-X and the trisomy 15 were present in different cell lines, gain of an X chromos ome occurred either in the same cell division as the trisomy 15 rescue or shortly before or after.