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The diagnosis of calpainopathy is obtained by identifying calpain-3 protein deficiency or CAPN3 gene mutations. However, in many patients with limb girdle muscular dystrophy type 2A (LGMD2A), the calpain-3 protein quantity is normal because loss-of-function mutations cause its enzymatic inactivation. The identification of such patients is difficult unless a functional test suggests pursuing a search for mutations.

Screening of calpain-3 autolytic activity in LGMD muscle: a functional map of CAPN3 gene mutations