Genotype ‐phenotype correlation in myotonic dystrophy

Abstract

Myotonic dystrophy (DM) is caused by a mutation in the length of a trinucleotide (CTG) repeat in the 3' untranslated region of the my‐otonin 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 several thousands of such repeats. Since no information on a genotype‐phenotype correlation in Austrian DM‐patients is available, we examined a small group of these patients for the unstable trinucleotide repeat. Molecular analysis was used to clarify equivocal clinical diagnoses and confirm clinical findings. We 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. Clinical assessment was based on the muscular disability rating scale (MDRS) and a sum of symptoms score (SSS). There was a significant correlation between the clinical scores (MDRS: Spearman r = 0.51: p = 0.029; SSS: Spearman r = 0.538; p = 0.0259) used and the size of the amplification of the trinucleotide repeat. The largest expansion found in our group of patients was 6 kb. Furthermore, we observed both expansion and contraction of the enlarged fragment during transmission from one generation to the next.