SARCOGLYCAN DEFICIENCY IN A LARGE ITALIAN POPULATION OF MYOPATHIC PATIENTS

Autosomal recessive limb-girdle muscular dystrophies are a heterogeneo us group of genetic diseases with a wide spectrum of clinical severity and age of onset; mutations in the gene encoding the dystrophin-assoc iated sarcoglycan proteins (alpha, beta, gamma and delta) have recentl y been shown to cause some cases of these myopathies (primary sarcogly canopathies, types 2D, 2E, 2C and 2F, respectively). In this study we have examined a large population of Italian myopathic patients to dete rmine the frequency of alpha-, beta- and gamma-sarcoglycan deficiency and to correlate molecular defects with clinical phenotypes; to exclud e the presence of primary dystrophinopathies both genetic and immunolo gical analysis of dystrophin was performed. We report 12 patients (10 male and 2 female) with deficiency of either one or mon sarcoglycan pr oteins. They were aged 8-56 years with onset between 4 and 30 years of age; they all presented with either mild, moderate or severe limb-gir dle involvement associated with elevated blood creatine kinase levels and myopathic pattern at EMC; one was also affected with a mild dilati on cardiomyopathy. All patients, except one, showed pathological muscl e histological changes. Absence of all three proteins always cell-elat es with severe forms, whereas mild protein deficiencies or isolated pa rtial alpha-sarcoglycan deficiency correlate with either severe, moder ate or mild forms.