Mutations in the skeletal muscle α-actin gene in patients with actin myopathy and nemaline myopathy

摘要: Muscle contraction results from the force generated between thin filament protein actin and thick myosin, which causes muscle filaments to slide past each other. There are skeletal muscle, cardiac smooth non-muscle isoforms of both myosin. Inherited diseases in humans have been associated with defects (dilated cardiomyopathy hypertrophic cardiomyopathy), myosin (hypertrophic cardiomyopathy) (deafness). Here we report that mutations human alpha-actin gene (ACTA1) two different diseases, 'congenital myopathy excess myofilaments' (actin myopathy) nemaline myopathy. Both characterized by structural abnormalities fibres variable degrees weakness. We identified 15 missense resulting 14 amino acid changes. The ACTA1 distributed throughout all six coding exons, some involve known functional domains actin. Approximately half patients died within their first year, but female survived into thirties children. dominant 1 families, being single heterozygous. only family showing inheritance comprised a 33-year-old affected mother her unaffected In another family, clinically father is somatic mosaic for mutation seen his recessive one siblings had heterozygous paternally other maternally inherited. also de novo seven sporadic probands it was possible analyse parental DNA.