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

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.