Genotype - Phenotype Correlations in Iranian Myotonic Dystrophy type I patients

Neda Moradin; Mojtaba Azimian; Bahareh Shojasaffar University of Social Welfare and Rehabilitation Sciences Ana Maria Cobo, - Centre de Référence Maladies Neuromusculaires GNMH, France Kaveh Alavi, Kariminejad-Najmabadi Pathology & Genetics Center Shahriar Nafisi, Shariati Hospital, Tehran Mandana Hasanzad, Seyed Mohammad Ebrahim Moosavi, Azadeh Shirazian, Hossein Najmabadi. Kimia Kahrizi University of Social Welfare and Rehabilitation Sciences, Genetics Research Center Abstract Myotonic Dystrophy type I (DM1) is a dominantly inherited disorder with a multisystemic pattern affecting skeletal muscle, heart, eye, endocrine and central nervous system. DM1 is associated with the expansion and instability of CTG repeat in the 3' untranslated region of the myotonic dystrophy protein kinase (DMPK) gene located on chromosome 19q13.3. The aim of this study was to determine clinical and genetic characteristic of DM1 in Iranian patients. Genotype-phenotype correlation was also assessed in a small group of studied patients. Twenty six DM1 patients belonging to seventeen families were analyzed. 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 diagnosis and in order to confirm clinical findings. There was an inverse and significant correlation between age of onset and expanded allele length (p=0.026, tau-b=-0.360) based on Kendall's tau-b correlation coefficient, while there was no significant correlation between age of onset and severity of the clinical symptoms (p<0.05). Also no significant correlation was observed between the two severity scales of the disease (MDRS and SSS) and expanded allele length (p<0.05). Expanded allele length was correlated with hypogonadism (p=0.007) and cognitive impairment (p=0.034). There was no correlation between cataract and endocrine dysfunction with the expansion size in DM1 patients. Generally it seems there is discordant correlation between clinical symptoms and expanded allele length.