LGMD2A: genotype-phenotype correlations based on a large mutational survey on the calpain 3 gene

Summary We present here the clinical, molecular and biochemical findings from 238 limb-girdle muscular dystrophy type 2A (LGMD2A) patients, representing � 50% (238 out of 484) ofthe suspected calpainopathycases referredforthemolecularstudyofthecalpain3(CAPN3)gene.Themeanageat onset of LGMD2A patients was � 14 years, and the first symptoms occurred between 6 and 18 years of age in 71% of patients. The mean age at which the patients became wheelchair bound was 32.2 years, with 84% requiring the use of a wheelchair between the age of 21 and 40 years. There was no correlation between the age at onset and the time at which the patient became wheelchair bound, nor between the sex of the patient and the risk of becoming wheelchair bound. Of the cases where the CAPN3 gene was not affected, � 20% were diagnosed as LGMD2I muscular dystrophy, while facioscapulohumeral musculardystrophy(FSHD)wasuncommoninthissample. We identified 105 different mutations in the CAPN3 gene of which 50 have not been described previously. These were distributed throughout the coding region of the gene, although some exons remained free of mutations. The most frequent mutation was 2362AG!TCATCT (exon 22), which was present in 30.7% of the chromosomes