Actin mutations are one cause of congenital fibre type disproportion.

Abstract

We report three heterozygous missense mutations of the skeletal muscle alpha actin gene (ACTA1) in three unrelated cases of congenital fiber type disproportion (CFTD) from Japan and Australia. This represents the first genetic cause of CFTD to be identified and confirms that CFTD is genetically heterogeneous. The three mutations we have identified Leucine221Proline, Aspartate292Valine, and Proline332Serine are novel. They have not been found previously in any cases of nemaline, actin, intranuclear rod, or rod-core myopathy caused by mutations in ACTA1. It remains unclear why these mutations cause type 1 fiber hypotrophy but no nemaline bodies. The three mutations all lie on one face of the actin monomer on the surface swept by tropomyosin during muscle activity, which may suggest a common pathological mechanism. All three CFTD cases with ACTA1 mutations had severe congenital weakness and respiratory failure without ophthalmoplegia. There were no clinical features specific to CFTD cases with ACTA1 mutations, but the presence of normal eye movements in a severe CFTD patient may be an important clue for the presence of a mutation in ACTA1.

• Authors: Nigel G Laing, Nigel F Clarke, Danielle E Dye, Khema Liyanage, Kendall R Walker, Yasuaki Kobayashi, Shuichi Shimakawa, Tohru Hagiwara, Robert Ouvrier, John C Sparrow, Ichizo Nishino, Kathryn N North, Ikuya Nonaka
• Journal: Annals of neurology (Ann Neurol) Vol. 56 Issue 5 Pg. 689-94 (Nov 2004) ISSN: 0364-5134 [Print] United States
• PMID: 15468086 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Actins
• Aspartic Acid
• Serine
• Proline
• Adenosine Triphosphatases
• Leucine
• Valine

Topics

• Actins (genetics)
• Adenosine Triphosphatases (metabolism)
• Aspartic Acid (genetics)
• Biopsy (methods)
• Child, Preschool
• DNA Mutational Analysis (methods)
• Female
• Heterozygote
• Humans
• Infant
• Infant, Newborn
• Leucine (genetics)
• Male
• Models, Molecular
• Muscle Fibers, Slow-Twitch (metabolism, pathology)
• Muscle, Skeletal (enzymology, pathology)
• Mutation, Missense
• Myopathies, Structural, Congenital (genetics)
• Proline (genetics)
• Sequence Analysis, Protein
• Serine (genetics)
• Valine (genetics)