MILD AND SEVERE MUSCULAR-DYSTROPHY CAUSED BY A SINGLE GAMMA-SARCOGLYCAN MUTATION

Autosomal recessive muscular dystrophy is genetically heterogeneous. O ne form of this disorder, limb-girdle muscular dystrophy type 2C (LGMD 2C), is prevalent in northern Africa and has been shown to be associa ted with a single mutation in the gene encoding the dystrophin-associa ted protein gamma-sarcoglycan, The previous mutation analysis of gamma -sarcoglycan required the availability of muscle biopsies. To establis h a mutation assay for genomic DNA, the intron-exon structure of the g amma-sarcoglycan gene was determined, and primers were designed to amp lify each of the exons encoding gamma-sarcoglycan. We studied a group of Brazilian muscular dystrophy patients for mutations in the gamma-sa rcoglycan gene. These patients were selected on the basis of autosomal inheritance and/or the presence of normal dystrophin and/or deficienc y of alpha-sarcoglycan immunostaining. Four of 19 patients surveyed ha d a single, homozygous mutation in the gamma-sarcoglycan gene. The mut ation identified in these patients, all of African-Brazilian descent, is identical to that seen in the North African population, suggesting that even patients of remote African descent may carry this mutation. The phenotype in these patients varied considerably, Of four families with an identical mutation, three have a severe Duchenne-like muscular dystrophy. However, one family has much milder symptoms, suggesting t hat other loci may be present that modify the severity of the clinical course resulting from gamma-sarcoglycan gene mutations.