Sarcoglycan deficiency in a large Italian population of myopathic patients

Autosomal recessive limb-girdle muscular dystrophies are a heterogeneous group of genetic diseases with a wide spectrum of clinical severity and age of onset; mutations in the gene encoding the dystrophin-associated sarcoglycan proteins (alpha, beta, gamma and delta) have recently been shown to cause some cases of these myopathies (primary sarcoglycanopathies, types 2D, 2E, 2C and 2F, respectively). In this study we have examined a large population of Italian myopathic patients to determine the frequency of (alpha-, beta- and gamma-sarcoglycan deficiency and to correlate molecular defects with clinical phenotypes; to exclude the presence of primary dystrophinopathies both genetic and immunological analysis of dystrophin was performed. We report 12 patients (10 male and 2 female) with deficiency of either one or more sarcoglycan proteins. 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-girdle involvement associated with elevated blood creatine kinase levels and myopathic pattern at EMG; one was also affected with a mild dilation cardiomyopathy. All patients, except one, showed pathological muscle histological changes. Absence of all three proteins always correlates with severe forms, whereas mild protein deficiencies or isolated partial alpha-sarcoglycan deficiency correlate with either severe, moderate or mild forms.