[Genotype-phenotype correlations in an iraninan myotonic dystrophy cohort]

ABSTRACT

Myotonic Dystrophy type I [DM1] the most common form of muscular dystrophy in adults affecting 1/800 individuals is a dominantly inherited disorder with a multi-systemic pattern affecting skeletal muscle, heart, eye, endocrine and central nervous system. DM1 is associated with the expansion and instability of a trinucleotide [CTG] repeat in the 3 untranslated region of the myotonic dystrophy protein kinase [DMPK] gene located on choromosome 19q13.3. The normal copy number is 5-37 CTG repeat whereas it is expanded in DM1 patients and the expansion size broadly correlates with the severity of the symptoms. The aim of this study was to determine the clinical and genetic characteristic of DM1 in Iranian patients for genotype-phenotype correlation methods. Clinical assessment was based on the muscular disability rating scale [MDRS] and a sum of symptoms score [SSS]. Molecular analysis [PCR and Southern blot] was used to clarify uncertain clinical diagnoses and confirm the clinical findings. Forty six patients from twenty five DM1 families were reviewed. In all the DM1 patients, the wide clinical symptoms confirmed the reported phenotypic vaiability of disorder. The range of CTG expansion of the mutated allele was 97-833 CTG repeats and an inverse correlation between age of onest and repeat length was observed. A clear relation between the size of the CTG repeat and the clinical disease score [MDRS] was found but not with SSS. No correlation was seen between the endocrine dysfunction and the expansion size in DM1 patients