title: Mutations and polymorphisms of the skeletal muscle alpha-actin gene (ACTA1).
abstract: The ACTA1 gene encodes skeletal muscle alpha-actin, which is the predominant actin isoform in the sarcomeric thin filaments of adult skeletal muscle, and essential, along with myosin, for muscle contraction. ACTA1 disease-causing mutations were first described in 1999, when a total of 15 mutations were known. In this article we describe 177 different disease-causing ACTA1 mutations, including 85 that have not been described before. ACTA1 mutations result in five overlapping congenital myopathies: nemaline myopathy; intranuclear rod myopathy; actin filament aggregate myopathy; congenital fiber type disproportion; and myopathy with core-like areas. Mixtures of these histopathological phenotypes may be seen in a single biopsy from one patient. Irrespective of the histopathology, the disease is frequently clinically severe, with many patients dying within the first year of life. Most mutations are dominant and most patients have de novo mutations not present in the peripheral blood DNA of either parent. Only 10% of mutations are recessive and they are genetic or functional null mutations. To aid molecular diagnosis and establishing genotype-phenotype correlations, we have developed a locus-specific database for ACTA1 variations (http://waimr.uwa.edu.au).
authors: Centre for Medical Research, University of Western Australia, Western Australian Institute for Medical Research, QEII Medical Centre, Western Australia, Australia. nlaing@cyllene.uwa.edu.au
authors: Nigel G
authors: NG
authors: Laing
authors: Danielle E
authors: DE
authors: Dye
authors: Carina
authors: C
authors: Wallgren-Pettersson
authors: Gabriele
authors: G
authors: Richard
authors: Nicole
authors: N
authors: Monnier
authors: Suzanne
authors: S
authors: Lillis
authors: Thomas L
authors: TL
authors: Winder
authors: Hanns
authors: H
authors: Lochmüller
authors: Claudio
authors: C
authors: Graziano
authors: Stella
authors: S
authors: Mitrani-Rosenbaum
authors: Darren
authors: D
authors: Twomey
authors: John C
authors: JC
authors: Sparrow
authors: Alan H
authors: AH
authors: Beggs
authors: Kristen J
authors: KJ
authors: Nowak
mesh_terms: D000199:Actins / Q000235:genetics* / Q000378:metabolism; D000483:Alleles; D030541:Databases, Genetic; D014644:Genetic Variation; D006801:Humans; D008958:Models, Molecular; D018482:Muscle, Skeletal / Q000378:metabolism*; D009135:Muscular Diseases / Q000235:genetics / Q000473:pathology; D009154:Mutation; D010641:Phenotype; D011110:Polymorphism, Genetic
chemical_list: D000199:Actins