Prenatal diagnosis of familial dysautonomia by analysis of linked CA-repeat polymorphisms on chromosome 9q31-q33.

Familial Dysautonomia (FD) is an autosomal recessive sensory neuropathy that affects about 1 in 3,700 individuals of Ashkenazi Jewish ancestry. The underlying biochemical and genetic defects are unknown, thereby precluding prenatal diagnosis in at-risk families. Recently, the FD gene (DYS) was mapped with strong linkage disequilibrium to polymorphic 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 DNA from appropriate family members was analyzed to construct haplotypes using informative CA repeat polymorphisms closely linked to and flanking the FD locus. The calculation of risk for the prenatal diagnoses was performed by linkage analysis. All seven FD families were informative 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 the reliable prenatal diagnosis of FD in families with a previously affected child.