Genetic variability and clinical spectrum of Chinese patients with limb-girdle muscular dystrophy type 2A

Muscle Nerve. 2012 Nov;46(5):723-9. doi: 10.1002/mus.23381. Epub 2012 Aug 24.

Abstract

Introduction: Previous studies of limb-girdle muscular dystrophy type 2A (LGMD2A) patients in many countries have suggested a heterogeneous genetic and clinical spectrum, but the genotypes and phenotypes of Chinese LGMD2A patients remain unclear.

Methods: We directly screened calpain-3 (CAPN3) in 18 Chinese Han subjects who exhibited severely reduced or completely absent calpain-3 expression, as determined by Western blot analysis. We subsequently analyzed genotype/phenotype correlations.

Results: Seventeen patients (94.4%) were identified who had at least 1 causative mutation. All 18 mutations were distributed along the entire gene, and 11 of the mutations were novel, including 4 missense mutations, 5 deletions, and 2 splicing mutations. The phenotypes of these Chinese LGMD2A patients varied from severe LGMD to distal myopathy, and even asymptomatic hyper-CK-emia.

Conclusions: No evidential correlation was found between the genotypes and phenotypes of the patients assessed in this study. Western blot analysis is still a useful diagnostic method when genetic analysis is unavailable.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Alternative Splicing / genetics
  • Asian People / genetics*
  • Calpain / deficiency
  • Calpain / genetics*
  • Female
  • Gene Deletion
  • Genetic Variation / genetics*
  • Humans
  • Male
  • Middle Aged
  • Muscle Proteins / deficiency
  • Muscle Proteins / genetics*
  • Muscular Dystrophies, Limb-Girdle / diagnosis
  • Muscular Dystrophies, Limb-Girdle / genetics*
  • Mutation / genetics
  • Mutation, Missense / genetics
  • Retrospective Studies
  • Young Adult

Substances

  • Muscle Proteins
  • CAPN3 protein, human
  • Calpain

Supplementary concepts

  • Limb-girdle muscular dystrophy type 2A