Mutations in the sarcoglycan genes in patients with myopathy

N Engl J Med. 1997 Feb 27;336(9):618-24. doi: 10.1056/NEJM199702273360904.


Background: Some patients with autosomal recessive limb-girdle muscular dystrophy have mutations in the genes coding for the sarcoglycan proteins (alpha-, beta-, gamma-, and delta-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 alpha-sarcoglycan was used to stain muscle-biopsy specimens from 556 patients with myopathy and normal dystrophin genes (the gene frequently deleted in X-linked muscular dystrophy). 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 muscle RNA, analysis involving single-strand conformation polymorphisms, and sequencing.

Results: Levels of alpha-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 alpha-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 alpha-sarcoglycan gene, 8 (16 percent) in the beta-sarcoglycan gene, and 4 (8 percent) in the gamma-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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Biopsy
  • Child
  • Cytoskeletal Proteins / deficiency
  • Cytoskeletal Proteins / genetics*
  • DNA Mutational Analysis
  • Dystroglycans
  • Humans
  • Male
  • Membrane Glycoproteins / deficiency
  • Membrane Glycoproteins / genetics*
  • Muscle, Skeletal
  • Muscular Dystrophies / classification
  • Muscular Dystrophies / genetics*
  • Mutation*
  • Myofibrils / ultrastructure
  • Neuromuscular Diseases / genetics*
  • Sarcoglycans


  • Cytoskeletal Proteins
  • DAG1 protein, human
  • Membrane Glycoproteins
  • Sarcoglycans
  • Dystroglycans