CLINICAL SPECTRUM AND MOLECULAR DIAGNOSIS OF ANGELMAN AND PRADER-WILLI-SYNDROME PATIENTS WITH AN IMPRINTING MUTATION

Recent studies have identified a new class of Prader-Willi syndrome (P WS) and Angelman syndrome (AS) patients who have biparental inheritanc e, but neither the typical deletion nor uniparental disomy (UPD) or tr anslocation, However, these patients have uniparental DNA methylation throughout 15q11-q13, and thus appear to have a mutation in the imprin ting process for this region, Here we describe detailed clinical findi ngs of five AS imprinting mutation patients (three families) and two P WS imprinting mutation patients (one new family), All these patients h ave essentially the classical clinical phenotype for the respective sy ndrome, except that the incidence of microcephaly is lower in imprinti ng mutation AS patients than in deletion AS patients, Furthermore, imp rinting mutation AS and PWS patients do not typically have hypopigment ation, which is commonly found in patients with the usual large deleti on, Molecular diagnosis of these cases is initially achieved by DNA me thylation analyses of the DN34/ZNF127, PW71 (D15S63), and SNRPN loci, The latter two probes have clear advantages in the simple molecular di agnostic analysis of PWS and AS patients with an imprinting mutation, as has been found for typical deletion or UPD PWS and AS cases, With t he recent finding of inherited microdeletions in PWS and AS imprinting mutation families, our studies define a new class of these two syndro mes, The clinical and molecular identification of these PWS and AS pat ients has important genetic counseling consequences. (C) 1997 Wiley-Li ss, Inc.