By the same authors

From the same journal

Actin mutations are one cause of congenital fibre type disproportion

Research output: Contribution to journalArticlepeer-review

Published copy (DOI)

Author(s)

  • N G Laing
  • N F Clarke
  • D E Dye
  • K Liyanage
  • K R Walker
  • Y Kobayashi
  • S Shimakawa
  • T Hagiwara
  • R Ouvrier
  • J C Sparrow
  • I Nishino
  • K N North
  • I Nonaka

Department/unit(s)

Publication details

JournalAnnals of neurology
DatePublished - Nov 2004
Issue number5
Volume56
Number of pages6
Pages (from-to)689-694
Original languageEnglish

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.

    Research areas

  • NEMALINE MYOPATHY, MUSCLE, GENE, ACTA1

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