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

Buiting K, Fa¨rber C, Kroisel P, Wagner K, Brueton L, Robertson ME,Lich C, Horsthemke B. Imprinting centre deletions in two PWSfamilies: implications for diagnostic testing and genetic counselling.Clin Genet 2000: 58: 284–290. © Munksgaard, 2000Prader–Willi syndrome (PWS) is a complex genetic syndrome involvingimprinted genes on chromosome 15. It is usually sporadic, and veryfew affected siblings have been described. Here, we report the clinicaland molecular findings in two families with a microdeletion affectingthe chromosome 15 imprinting centre (IC). Carrier males have a 50%risk of having children with an imprinting defect leading to PWS, andin one of the two families, a father has two affected daughters. In theother family, diagnostic testing was confounded by the presence of aneutral microdeletion close to the IC. The silent transmission of PWSIC deletions through the female germline and the occurrence of neutralmicrodeletions close to the IC can impose considerable problems ondiagnostic testing and genetic counselling in affected families.