Mutations in the sarcoglycan genes in patients with myopathy

Background: Some patients with autosomal recessive limb-girdle muscular dystrophy have mutations in the genes coding for the sarcoglycan proteins (α-, β-, γ-, and δ-sarcoglycan). To determine the frequency of sarcoglycan gene mutations and the relation between the clinical features and genotype, we studied several hundred patients with myopathy. Methods: Antibody against α-sarcoglycan was used to stain muscle-biopsy specimens from 566 patients with myopathy and normal dystrophin genes (the gene frequently deleted in X-linked muscular dystrophy). Patients whose biopsy specimens showed a deficiency of α-sarcoglycan on immunostaining were studied for mutations of the α-, β-, and γ-sarcoglycan genes with reverse transcription of muscle RNA, analysis involving single-strand conformation polymorphisms, and sequencing. Results: Levels of α-sarcoglycan were found to be decreased on immunostaining of muscle-biopsy specimens from 54 of the 556 patients (10 percent); in 25 of these patients no α-sarcoglycan was detected. Screening for sarcoglycan gene mutations in 50 of the 54 patients revealed mutations in 29 patients (58 percent): 17 (34 percent) had mutations in the α-sarcoglycan gene, 8 (16 percent) in the β-sarcoglycan gene, and 4 (8 percent) in the γ-sarcoglycan gene. No mutations were found in 21 patients (42 percent). The prevalence of sarcoglycan-gene mutations was highest among patients with severe (Duchenne-like) muscular dystrophy that began in childhood (18 of 83 patients, or 22 percent); the prevalence among patients with proximal (limb-girdle) muscular dystrophy with a later onset was 6 percent (11 of 180 patients). Conclusions: Defects in the genes coding for the sarcoglycan proteins are limited to patients with Duchenne-like and limb girdle muscular dystrophy with normal dystrophin and occur in 11 percent of such patients.