Mutations and polymorphisms of the skeletal muscle Î±-actin gene (<i>ACTA1</i>)

Laing, Nigel G.; Dye, Danielle E.; Wallgren‐Pettersson, Carina; Richard, Gabriele; Monnier, Nicole; Lillis, Suzanne; Winder, Thomas; Lochmüller, Hanns; Graziano, Claudio; Mitrani-Rosenbaum, Stella; Twomey, Darren; Sparrow, John C.; Beggs, Alan H.; Nowak, Kristen J.

doi:10.1002/humu.21059

Cited by 208 publications

(184 citation statements)

References 84 publications

Supporting

Mentioning

176

Contrasting

Unclassified

Order By: Relevance

“…4 All previously described patients with recessive ACTA1 disease (B10% of ACTA1 patients) have had functional 'null' variants and make no a-skeletal actin. 1,4,5 All have had severe congenital nemaline myopathy and survival after birth is only possible due to persistence of cardiac a-actin in the skeletal muscle of these children. 5 We describe the first recessive ACTA1 variant associated with expression of a-skeletal actin in skeletal muscle and survival well into adulthood.…”

Section: Discussionmentioning

confidence: 99%

Recessive ACTA1 variant causes congenital muscular dystrophy with rigid spine

et al. 2014

View full text Add to dashboard Cite

Variants in ACTA1, which encodes a-skeletal actin, cause several congenital myopathies, most commonly nemaline myopathy. Autosomal recessive variants comprise approximately 10% of ACTA1 myopathy. All recessive variants reported to date have resulted in loss of skeletal a-actin expression from muscle and severe weakness from birth. Targeted next-generation sequencing in two brothers with congenital muscular dystrophy with rigid spine revealed homozygous missense variants in ACTA1. Skeletal a-actin expression was preserved in these patients. This report expands the clinical and histological phenotype of ACTA1 disease to include congenital muscular dystrophy with rigid spine and dystrophic features on muscle biopsy. This represents a new class of recessive ACTA1 variants, which do not abolish protein expression.

show abstract

Section: Discussionmentioning

confidence: 99%

Recessive ACTA1 variant causes congenital muscular dystrophy with rigid spine

et al. 2014

View full text Add to dashboard Cite

show abstract

“…12 Of these, most variants are dominant, missense, and have arisen de novo. 13 About 10% are recessive variants. Most recessive variants are genetic or functional null variants 13 but recently recessive ACTA1 disease with retention of skeletal muscle actin expression was described in a family presenting with a rigid spine syndrome.…”

Section: Mutational Spectrummentioning

confidence: 99%

“…13 About 10% are recessive variants. Most recessive variants are genetic or functional null variants 13 but recently recessive ACTA1 disease with retention of skeletal muscle actin expression was described in a family presenting with a rigid spine syndrome. 14 Dominant inheritance is less common, and only seen in families with a milder phenotype.…”

Section: Mutational Spectrummentioning

confidence: 99%

See 1 more Smart Citation

Clinical utility gene card for: Nemaline myopathy – update 2015

et al. 2015

Self Cite

View full text Add to dashboard Cite

“…It is worth noting that the second mutation, M49V, has previously been described for the skeletal isoform of a-actin (encoded by the gene ACTA1) in patients with nemaline or cap-type congenital myopathy. 13,14 All three mutations were absent from 192 control chromosomes and were not listed in the GenBank dbSNP library. The mutation R39C was predicted to have benign consequences by the PolyPhen program, but it was called 'deleterious' by the program PANTHER.…”

Section: Detection Of Three Novel Mutations In the Acta2 Genementioning

confidence: 99%

Three novel mutations in the ACTA2 gene in German patients with thoracic aortic aneurysms and dissections

Hoffjan¹,

Waldmüller²,

Blankenfeldt³

et al. 2011

Eur J Hum Genet

View full text Add to dashboard Cite

Mutations in the gene encoding smooth muscle cell alpha actin (ACTA2) have recently been shown to cause familial thoracic aortic aneurysms leading to type A dissections (TAAD) and predispose to premature stroke and coronary artery disease. In order to further explore the role of ACTA2 variations in the pathogenesis of TAAD, we sequenced the coding regions of this gene in 40 unrelated German patients with TAAD (with (n¼21) or without (n¼19) clinical features suggestive of Marfan syndrome). All patients had previously tested negative for mutations in the FBN1 and TGFBR2 genes. We identified three novel ACTA2 mutations and mapped them on a three-dimensional model of actin. Two mutations affect residues within (M49V) or adjacent to (R39C), the DNAse-I-binding loop within subdomain 2 of alpha actin. They were observed in families with recurrent aortic aneurysm (R39C) or aortic dissection (M49V). The third mutation causes an exchange in the vicinity of the ATP-binding site (G304R) in a patient thought to have isolated TAAD. None of the affected individuals had clinical features typical for Marfan syndrome, and no case of premature stroke or coronary artery disease was reported from the affected families. In conclusion, we underscore the role of ACTA2 mutations in nonsyndromic TAAD and suggest that ACTA2 should be included in the genes routinely investigated for syndromic and nonsyndromic TAAD. Detailed clinical investigations of additional families are warranted to further explore the full range of phenotypic signs associated with the three novel mutations described here.

show abstract

Mutations and polymorphisms of the skeletal muscle Î±-actin gene (ACTA1)

Cited by 208 publications

References 84 publications

Recessive ACTA1 variant causes congenital muscular dystrophy with rigid spine

Recessive ACTA1 variant causes congenital muscular dystrophy with rigid spine

Clinical utility gene card for: Nemaline myopathy – update 2015

Three novel mutations in the ACTA2 gene in German patients with thoracic aortic aneurysms and dissections

Contact Info

Product

Resources

About