MOLECULAR DIAGNOSIS OF HOMOZYGOUS MYOTONIC-DYSTROPHY IN 2 ASYMPTOMATIC SISTERS

The genetic defect underlying myotonic dystrophy (DM) has been identif ied as the expansion of an unstable trinucleotide repeat sequence, and this discovery has led to new approaches to diagnosis and genetic cou nselling in families with the disorder. We report the genetic analysis of a consanguineous DM family in which two asymptomatic sisters had b een shown to be homozygous for the 'at risk' haplotype. PCR analysis o f the region spanning the trinucleotide expansion demonstrated that bo th sisters possessed two alleles with repeat sizes normally seen in mi nimally affected patients. Extensive clinical examination failed to de monstrate any of the symptoms of DM in these women. The implications o f this finding, both for understanding the disease mechanism, and for genetic counselling in such situations are discussed.