GENOTYPE-PHENOTYPE CORRELATION IN MYOTONIC-DYSTROPHY

Myotonic dystrophy (DM) is caused bq a mutation in the length of a tri nucleotide (CTG) repeat in the 3' untranslated region of the myotonin protein kinase gene located on chromosome 19q13.3 The normal gene has between 5 and 36 CTG trinucleotide repeats. whereas minimally affected individuals have 50 copies and severely affected DM-patients have sev eral thousands of such repeats, Since no information on a genotype-phe notype correlation in Austrian DM-patients is available. we explained a small group of these patients for the unstable trinucleotide repeat. Molecular analysis was used to clarify equivocal clinical diagnoses a nd confirm clinical findings. Ne studied eight DM-families, a total of 57 individuals, of whom 18 were diagnosed with a trinucleotide repeat expansion. Twenty-six unrelated individuals served as a control. Clin ical assessment tvas based on the muscular disability rating scale (MD RS) and a aunt of symptoms score (SSS). There was a significant correl ation between the clinical stores (MDRS: Spearman r = 0.51; p = 0.029: SSS: Spearman r = 0.538; p = 0.0259) used and the size of the amplifi cation of the trinucleotide repeat, The largest expansion found in our group of patients was 6 kb. Furthermore we observed both expansion an d contraction of the enlarged fragment during transmission from one ge neration to the next.