Mutations in the sarcoglycan genes in patients with myopathy

David J. Duggan, J. Rafael Gorospe, Marina Fanin, Eric P. Hoffman, Corrado Angelini, E. Pegoraro, S. Noguchi, E. Ozawa, W. Pendlebury, A. J. Waclawik, D. A. Duenas, I. Hausmanowa-Petrusewicz, A. Fidzianska, S. C. Bean, J. S. Haller, J. Bodensteiner, C. M. Greco, A. Pestronk, A. Berardinelli, D. F. GelinasH. Abram, R. W. Kuncl

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)618-624
Number of pages7
JournalNew England Journal of Medicine
Volume336
Issue number9
DOIs
Publication statusPublished - Feb 27 1997

ASJC Scopus subject areas

  • Medicine(all)

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