CYTOGENETIC AND AGE-DEPENDENT RISK-FACTORS ASSOCIATED WITH UNIPARENTAL DISOMY-15

Prader-Willi syndrome (PWS) results primarily from either a paternal d eletion of 15q11-q13 or maternal uniparental disomy (UPD) of chromosom e 15. Including the present and published cases, more than 120 patient s with maternal UPD of human chromosome 15 have been ascertained. Inve stigation of chromosome 15 markers indicates that approximately 71 per cent of the additional maternal chromosomes were the result of meiosi s I segregation errors, 13 per cent were the result of meiosis II erro rs, and 16 per cent resulted from post-zygotic duplication of one chro mosome 15. An increase in maternal age is associated with UPD cases du e to meiotic errors. The age-specific risk for UPD(15) is analysed and shows an exponential increase with maternal age which is similar to t hat observed for trisomy 21. For women greater than or equal to 40 yea rs of age, the risk for UPD(15) is approximately 1/3400 livebirths. Th e frequency of chromosome aberrations associated with UPD(IS) is also discussed. Two types of aberrations are at significantly increased ris k of fetal UPD(IS): de novo (or inherited) isochromosome 15 and confin ed placental mosaicism for trisomy 15. Two additional abnormalities, t ie novo small marker chromosomes derived from 15, e.g., idic15(pter-q1 1:q11-pter), and familial Robertsonian translocations involving chromo some 15; appear to have a mildly increased risk of UPD(15).