Muscle disease caused by mutations in the skeletal muscle alpha-actin gene (ACTA1)

@article{Sparrow2003MuscleDC,
  title={Muscle disease caused by mutations in the skeletal muscle alpha-actin gene (ACTA1)},
  author={John C. Sparrow and Kristen J. Nowak and Hayley J. Durling and Alan H. Beggs and Carina Wallgren‐Pettersson and Norma B Romero and Ikuya Nonaka and Nigel G. Laing},
  journal={Neuromuscular Disorders},
  year={2003},
  volume={13},
  pages={519-531}
}

Figures and Tables from this paper

Mutations and polymorphisms of the skeletal muscle α‐actin gene (ACTA1)

The ACTA1 gene encodes skeletal muscle α‐actin, which is the predominant actin isoform in the sarcomeric thin filaments of adult skeletal muscle, and essential, along with myosin, for muscle contraction, which results in five overlapping congenital myopathies: nemalineMyopathy; intranuclear rod myopathy; actin filament aggregate myopathy%; congenital fiber type disproportion; and myopathy with core‐like areas.

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Skeletal muscle α-actin diseases (actinopathies): pathology and mechanisms

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! 1 ! Skeletal muscle α-actin diseases-“ actinopathies ”

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Actin myopathy with nemaline bodies, intranuclear rods, and a heterozygous mutation in ACTA1 (Asp154Asn)

No developmental abnormalities of the central nervous system, and no loss of spinal motor neurons were detected despite atrophy or hypotrophy of a considerable number of muscle fibers, and the peripheral nervous system showedNo loss of motor or sensory myelinated fibers andno loss of sensory neurons in spinal ganglia.

Heterogeneity of nemaline myopathy cases with skeletal muscle α‐actin gene mutations

Clinical and pathological features associated with 29 ACTA1 mutations found in 38 individuals from 28 families are described, accounting for more than half of severe cases and 26% of all NM cases in this series.

Functional Effects of Nemaline Myopathy Mutations on Human Skeletal α-Actin*

None of the three mutations affected the folding of the actin monomer, the velocity at which skeletal myosin moves actin in an in vitro motility assay, or the relative average isometric force supported by F-actin, and defects in fundamental actomyosin interactions are unlikely to account for the muscle weakness observed in affected patients.
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The marked variability, in clinical phenotype, among patients with different mutations in ACTA1 suggests that both the site of the mutation and the nature of the amino acid change have differential effects on thin-filament formation and protein-protein interactions.

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