The pathogenesis of ACTA1‐related congenital fiber type disproportion

@article{Clarke2007ThePO,
  title={The pathogenesis of ACTA1‐related congenital fiber type disproportion},
  author={Nigel F. Clarke and Biljana Ilkovski and Sandra T. Cooper and Valentina A. Valova and Phillip J. Robinson and Ikuya Nonaka and Juan-Juan Feng and Steven B Marston and Kathryn N. North},
  journal={Annals of Neurology},
  year={2007},
  volume={61}
}
Mutations in ACTA1 have been associated with a variety of changes in muscle histology that likely result from fundamental differences in the way that ACTA1 mutations disrupt muscle function. Recently, we reported three patients with congenital fiber type disproportion (CFTD) caused by novel heterozygous missense mutations in ACTA1 (D292V, L221P, P332S) with marked type 1 fiber hypotrophy as the only pathological finding on muscle biopsy. We have investigated the basis for the histological… 

Mutations in TPM3 are a common cause of congenital fiber type disproportion

This work investigated whether mutation of TPM3 is a cause of CFTD, and found that the gene encoding α‐tropomyosinslow (TPM3) is a rare cause of nemaline myopathy.

A case of congenital fiber‐type disproportion syndrome presenting dilated cardiomyopathy with ACTA1 mutation

The case of a 10‐year‐old boy presenting with CFTD and DCM is reported, including one patient with dilated cardiomyopathy (DCM), who has previously been reported.

Genotype–phenotype correlations in ACTA1 mutations that cause congenital myopathies

Congenital myopathies – a comprehensive update of recent advancements

Through this review, this work provides an up‐to‐date analysis of congenital myopathies including clinical and pathologic aspects.

Congenital fiber-type disproportion.

  • N. Clarke
  • Medicine
    Seminars in pediatric neurology
  • 2011

Intranuclear rod myopathy: molecular pathogenesis and mechanisms of weakness

Mutations in the α‐skeletal actin gene (ACTA1) result in a variety of inherited muscle disorders characterized by different pathologies and variable clinical phenotypes, including intranuclear rod myopathy and muscle weakness.

What’s new in congenital myopathies?

  • K. North
  • Medicine
    Neuromuscular Disorders
  • 2008

Uwa Research Publication

Headway is being made in terms of developing therapeutics for ACTA1 disease, with gene therapy (specifically reducing the amount of mutant skeletal muscle α-actin protein) and pharmacological agents showing promising results in animal models and patient muscle.
...

References

SHOWING 1-10 OF 29 REFERENCES

Missense mutations of ACTA1 cause dominant congenital myopathy with cores

Minicores and central cores have been detected concomitantly as well as separately in successive muscle biopsy specimens of single patients and in myofibers of different affected family members.

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.

Actin mutations are one cause of congenital fibre type disproportion

The presence of normal eye movements in a severe CFTD patient may be an important clue for the presence of a mutation in ACTA1, and three heterozygous missense mutations of the skeletal muscle alpha actin gene (ACTA1) in three unrelated cases of congenital fiber type disproportion are reported.

Heterogeneity of nemaline myopathy cases with skeletal muscle alpha-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.

Nemaline Myopathy Caused by Mutations in the Muscle α-Skeletal-Actin Gene

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.

Nemaline myopathy caused by mutations in the muscle alpha-skeletal-actin gene.

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.

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

Clinical course correlates poorly with muscle pathology in nemaline myopathy

Nemaline myopathy due to mutations in α-tropomyosinSLOW was characterized by preferential rod formation in, and atrophy of, type 1 fibers, which varied widely in families with multiple affected members.

Myopathy mutations in α-skeletal-muscle actin cause a range of molecular defects

A range of defects and behaviors of the mutants in vitro and in cultured cells are found, paralleling the complexity of actin-based muscle myopathy phenotypes.