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 prot eins (alpha-, beta-, gamma-, and delta-sarcoglycan). To determine the frequency of sarcoglycan-gene mutations and the relation between the c linical features and genotype, we studied several hundred patients wit h myopathy. Methods Antibody against alpha-sarcoglycan was used to sta in muscle-biopsy specimens from 556 patients with myopathy and normal dystrophin genes (the gene frequently deleted in X-linked muscular dys trophy). Patients whose biopsy specimens showed a deficiency of alpha- sarcoglycan on immunostaining were studied for mutations of the alpha- , beta-, and gamma-sarcoglycan genes with reverse transcription of mus cle RNA, analysis involving single-strand conformation polymerphisms, and sequencing, Results Levels of alpha-sarcoglycan were found to be d ecreased on immunostaining of muscle-biopsy specimens from 54 of the 5 56 patients (10 percent); in 25 of these patients no alpha-sarcoglycan was detected. Screening for sarcoglycan-gene mutations in 50 of the 5 4 patients revealed mutations in 29 patients (58 percent): 17 (34 perc ent) had mutations in the alpha-sarcoglycan gene, 8 (16 percent) in th e beta-sarcoglycan gene, and 4 (8 percent) in the gamma-sarcoglycan ge ne. No mutations were found in 21 patients (42 percent). The prevalenc e 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 sarc oglycan proteins are limited to patients with Duchenne-like and limb-g irdle muscular dystrophy with normal dystrophin and occur in 11 percen t of such patients. (C) 1997, Massachusetts Medical Society.