Missense mutations of ACTA1 cause dominant congenital myopathy with cores

Abstract
The increased number of identified genetic defects in patients with thoroughly characterised CM phenotypes has disclosed both marked phenotype and genotype variability and considerable disease overlap. The finding of cores together with rod-like lesions in muscle biopsy specimens of patients with RYR1 mutations and skeletal muscle alpha-actin gene (ACTA1; MIM 102610) mutations and in families showing linkage to chromosome 15q21–q23 indicate a phenotype overlap of core diseases and nemaline myopathy (MIM 256030).8– 14 Likewise, the concurrent occurrence of cores and fingerprint bodies suggests an overlap with fingerprint body myopathy (MIM 305550).15 These findings and an absence of mutations in established gene loci in patients with clinical and histological hallmarks of core myopathy promise further genetic heterogeneity.