Résumé :
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Communication n° 466 Introduction : Myotonic dystrophy type 1 (DM1) is a diffuse systemic disorder in which the most prominent features, i. e. myotonia and muscular atrophy may be accompanied by cataracta, gonadal atrophy, endocrine abnormalities, heart conduction defects and mental deficit. It is inherited as an autosomal dominant trait with a variable penetrance. An unstable expansion of (CTG)n repeats in the 3' untranslated region encoding a member of the protein kinase family in 19q13.3 is the causative mutation for myotonic dystrophy. Healthy individuals harbour 5-37 CTG repeats, whereas in affected individuals repeat expansion varies between 37 and 4000. Objectives and methods : To examine the correlation between clinical expression and CTG trinucleotide repeat length, radioactive PCR as well as Southern blot analyses using probe p5B1.4 were carried out in families clinically diagnosed with myotonic dystrophy. Results : So far, 28 patients from 14 families were analysed and in 11 cases the mutation in DMPK gene was confirmed. The expanded CTG repeats were transmitted maternally as well as paternally. In the maternally transmitted cases the expanded fragment lengths were always larger than in the paternally transmitted ones. Moreover, a clear correlation was established between phenotype severity and the length of the CTG expansion. Longer expansions resulted in earlier onset of the symptoms. Phenotypes varied between congenital onset, classical forms and mild symptoms even within the same family corresponding to the size of the expansion. Conclusion : The newly introduced molecular technique in Hungarian families with clinical suspicion of dystrophia myotonica improved the differential diagnosis of this neuromuscular disorder. Furthermore, the knowledge of the molecular background enabled us to explain the phenotypic variation of the disease.
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