Molecular diagnosis of homozygous myotonic dystrophy in two asymptomatic sisters.

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