Actin mutations are one cause of congenital fibre type disproportion
Actin mutations are one cause of congenital fibre type disproportion
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DOI：
10.1002/ana.20260
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发表时间：
2004-11-01
影响因子：
11.2
通讯作者：
Nonaka, I
中科院分区：
文献类型：
--
作者：
Laing, NG;Clarke, NF;Nonaka, I
我们报告了三个杂合错义突变的骨骼肌α -肌动蛋白基因（ACTA1）在三个不相关的先天性纤维型失调（CFTD）在日本和澳大利亚的病例。这代表了CFTD的第一个被确定的遗传原因，并证实了CFTD是遗传异质性的。我们鉴定的三个突变Leucine221Proline， Aspartate292Valine和Proline332Serine是新的。以前在由ACTA1突变引起的线状、肌动蛋白、核内棒状或棒状核肌病的任何病例中未发现它们。目前尚不清楚为什么这些突变导致1型纤维萎缩而没有线状体。这三种突变都位于肌动蛋白单体的一个表面，在肌肉活动时被原肌球蛋白扫过，这可能提示一个共同的病理机制。3例ACTA1突变的CFTD患者均有严重的先天性虚弱和呼吸衰竭，无眼麻痹。ACTA1突变的CFTD病例没有特异性的临床特征，但严重CFTD患者正常眼动的存在可能是ACTA1突变存在的重要线索。
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.