Molecular prenatal diagnosis of ataxia telangiectasia heterozygosity by direct mutational assays

Ataxia telangiectasia (AT) is a severe autosomal recessive disease, rare bu t not infrequent in Italy. Owing to the seriousness of the disease, prenata l diagnosis has been attempted in the past by means of cytogenetic, biochem ical, radio-biological and indirect molecular analyses. We performed the fi rst direct molecular prenatal diagnosis of AT on a chorionic villi sample f rom a 37-year-old woman at the 10th week of pregnancy. She had two previous children suffering AT and two induced abortions, At molecular analysis her affected children were compound heterozygotes for mutations 7792C-->T in e xon 55 (from the mother) and 8283delTC in exon 59 (from the father). The pr enatal diagnosis was performed by two different operators in double-blind f orm. Mutation 7792C-->T was studied by restriction enzyme analysis using Ta qI. Mutation 8283delTC was screened by heteroduplex analysis. The fetus: wa s heterozygous for the mutation 7792C-->T (confirmed by sequencing). In ord er to verify the possible contamination by maternal DNA, polymorphic loci H LA-DRB1 and HLA-DQA1, together with microsatellite markers D6S259, D11S2000 , D11S29, D11S1778 and D11S2179, were examined. All these loci were informa tive,: showing that the fetus received only one allele from each parent. Th e heterozygosity for ATM mutation 7792-->T was confirmed by molecular studi es after the birth of a healthy male baby. Copyright (C) 1999 John Wiley & Sons, Ltd.