PRENATAL DIAGNOSTIC TESTING FOR FAMILIAL DYSAUTONOMIA USING LINKED GENETIC-MARKERS

Familial dysautonomia (FD), a recessively inherited disease, has been mapped to chromosome 9q31. Highly polymorphic dinucleotide repeat mark ers flanking the genetic locus and at the same genetic location have b een identified. We describe the prenatal diagnosis of FD using linkage and linkage disequilibrium analyses with these markers. Twelve famili es were analysed for informativeness and of these, seven went on to ha ve prenatal testing (a total of eight fetuses tested). All of these fe tuses were predicted to be heterozygous unaffected (FD carriers). Seve n fetuses have come to term and are normal. In the absence of a recomb inant proband, a panel of three proximal and three distal markers is s ufficient to provide informative flanking markers and an 87-96 per cen t likelihood of a highly predictive test. In an additional family at 1 :4 risk for FD, no DNA was available from the propositus. This family was analysed using linkage disequilibrium to the #18 allele of the tig htly linked marker D9S58 in conjunction with linkage analysis using da ta from two unaffected children. Prenatal diagnosis in this family ind icated an affected fetus.