Imprinting centre deletions in two PWS families: implications for diagnostic testing and genetic counselling

Prader-Willi syndrome (PWS) is a complex genetic syndrome involving imprint ed genes on chromosome 15. It is usually sporadic, and very few affected si blings have been described. Here, we report the clinical and molecular find ings in two families with a microdeletion affecting the chromosome 15 impri nting centre (IC). Carrier males have a 50% risk of having children with an imprinting defect leading to PWS, and in one of the two families, a father has two affected daughters. In the other family, diagnostic testing was co nfounded by the presence of a neutral microdeletion close to the IC. The si lent transmission of PWS IC deletions through the female germline and the o ccurrence of neutral microdeletions close to the IC can impose considerable problems on diagnostic testing and genetic counselling in affected familie s.