PRENATAL-DIAGNOSIS OF FAMILIAL DYSAUTONOMIA BY ANALYSIS OF LINKED CA-REPEAT POLYMORPHISMS ON CHROMOSOME 9Q31-Q33

Familial Dysautonomia (FD) is an autosomal recessive sensory neuropath y that affects about 1 in 3,700 individuals of Ashkenazi Jewish ancest ry, The underlying biochemical and genetic defects are unknown, thereb y precluding prenatal diagnosis in at-risk families, Recently, the FD gene (DYS) was mapped with strong linkage disequilibrium to polymorphi c markers in the chromosome 9 region q31-q33. In this report, the use of these markers for the prenatal diagnosis of FD by linkage analysis in families with a previously affected child was evaluated, Genomic DN A hom appropriate family members was analyzed to construct haplotypes using informative CA repeat polymerphisms closely linked to and flanki ng the FD locus. The calculation of risk for the prenatal diagnoses wa s performed by linkage analysis. All seven FD families were informativ e for the closely linked polymorphic markers and fetal diagnoses were made in eight pregnancies, Six fetal diagnoses were predicted with >98 % accuracy, while two with recombinations were predicted with at least 88% and 92% accuracy, Use of these closely linked markers permitted t he reliable prenatal diagnosis of FD in families with a previously aff ected child. (C) 1995 Wiley-Liss, Inc.