COUNSELING DILEMMAS ASSOCIATED WITH THE MOLECULAR CHARACTERIZATION OF2 ANGELMAN-SYNDROME FAMILIES

We report the molecular characterisation of two families with Angelman syndrome referred for prenatal diagnosis, in which atypical molecular findings resulted in counselling dilemmas. The first is a familial ca se of Angelman syndrome in which the two affected children have mutati ons which affect the imprinting mechanism, as shown by the presence of paternal DNA methylation patterns at D15S63 and SNRPN and biparental inheritance of 15q11-q13 markers. DNA prepared from a 21 week fetal bl ood sample detected a fetus with normal maternal and paternal DNA meth ylation patterns at D15S63, but inheritance of the same maternal chrom osome 15q11-q13 as the two affected sibs. This is probably a result of germline mosaicism in the mother. The second is a case of Angelman sy ndrome with an atypical deletion of 15q11-q13, which involves both unu sual proximal and distal breakpoints. The deletion was characterised i n order to assess the risk of Angelman syndrome in a second pregnancy in the mother of this child.