MYOTONIC-DYSTROPHY PHENOTYPE WITHOUT EXPANSION OF (CTG)N REPEAT - AN ENTITY DISTINCT FROM PROXIMAL MYOTONIC MYOPATHY (PROMM)

Myotonic dystrophy (DM) is associated with an expansion of an unstable (CTC)n repeat in the 3' untranslated region of the DM protein kinase (DMPK) gene on chromosome 19q13.3. We studied six patients from two fa milies who showed no expansions of the repeat, in spite of their clini cal diagnosis of DM. These patients had multi-systemic manifestations that were distinguishable from those seen in other myotonic disorders, including proximal myotonic myopathy (PROMM). In one additional famil y, two symptomatic members showed no expanded (CTG)n repeats, while th eir affected relatives had the expanded repeats. DM haplotype analysis failed to exclude the DMPK locus as a possible site of mutation in ea ch family; however, DMPK mRNA levels were normal. We conclude that a m utation(s) other than the expanded (CTG)n repeat can cause the DM phen otype. The mutation(s) in these families re main(s) to be mapped and c haracterized.