CAPN3 mutations in patients with idiopathic eosinophilic myositis

Objective Eosinophilic myositis (EM) constitutes a rare pathological entity characterized by eosinophilic infiltration of skeletal muscles, usually associated with parasite infections, systemic disorders, or the intake of drugs or L-tryptophan. The exclusion of such causes defines the spectrum of idiopathic EM. Based on a protein analysis performed in one affected patient, we identified the gene encoding calpain-3, CAPN3, as a candidate for a subset of idiopathic EM. Methods We screened CAPN3 for mutations using DHPLC and direct sequencing in six unrelated patients, recruited for EM diagnosed after histological examination of muscle biopsy samples, without any identified causative factor. Results We identified CAPN3 mutations in the six unrelated patients originally diagnosed with idiopathic EM. Interpretation Mutations in CAPN3 can cause EM. Thus, a subset of idiopathic EM is genetically determined, with an autosomal recessive mode of inheritance. Patients presented with a triad that appears to be indicative of CAPN3 mutations: (1) EM in the first decade, (2) elevated serum creatine phosphokinase levels (isolated or with little corresponding weakness), and (3) inconstant peripheral hypereosinophilia. However, that EM represents a distinct phenotype associated to CAPN3 mutations or, rather, an early histopathological picture of LGMD2A must be further evaluated. Our findings should be of interest toward further investigating the role of calpain-3 in skeletal muscle. Furthermore, patients with idiopathic EM should undergo calpain-3 protein analysis and be considered for subsequent molecular analysis of the CAPN3 gene.