Congenital myopathy is caused by mutation of HACD1.
Congenital myopathy is caused by mutation of HACD1.
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DOI：
10.1093/hmg/ddt380
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发表时间：
2013-12-20
影响因子：
3.5
通讯作者：
Parvari R
中科院分区：
文献类型：
--
作者：
Muhammad E;Reish O;Ohno Y;Scheetz T;Deluca A;Searby C;Regev M;Benyamini L;Fellig Y;Kihara A;Sheffield VC;Parvari R
先天性肌病是一种异质性遗传性肌肉疾病，其特征在于一系列独特的组织学异常。我们研究了一个先天性肌病的近亲家系。全基因组连锁分析和全外显子组测序鉴定了受影响个体中3-羟酰辅酶A脱氢酶1（HACD 1）的纯合无义突变。该突变导致患者肌肉中HACD 1 mRNA的无义介导衰减至对照水平的31%，并完全消除了3-羟酰基-CoA脱水的酶活性，这是极长链脂肪酸（VLCFA）延伸的第三步。我们描述了一个基因的有害突变相关的临床发现，以前不知道是与人类先天性肌病。我们认为，HACD 1基因突变导致VLCFA合成减少，VLCFA是膜脂质的组成部分，参与生理过程，导致先天性肌病。这些数据表明，HACD 1是肌肉功能所必需的。
Congenital myopathies are heterogeneous inherited diseases of muscle characterized by a range of distinctive histologic abnormalities. We have studied a consanguineous family with congenital myopathy. Genome-wide linkage analysis and whole-exome sequencing identified a homozygous non-sense mutation in 3-hydroxyacyl-CoA dehydratase 1 (HACD1) in affected individuals. The mutation results in non-sense mediated decay of the HACD1 mRNA to 31% of control levels in patient muscle and completely abrogates the enzymatic activity of dehydration of 3-hydroxyacyl-CoA, the third step in the elongation of very long-chain fatty acids (VLCFAs). We describe clinical findings correlated with a deleterious mutation in a gene not previously known to be associated with congenital myopathy in humans. We suggest that the mutation in the HACD1 gene causes a reduction in the synthesis of VLCFAs, which are components of membrane lipids and participants in physiological processes, leading to congenital myopathy. These data indicate that HACD1 is necessary for muscle function.
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影响因子：
4.8
作者：
Kihara, Akio;Sakuraba, Hiroko;Igarashi, Yasuyuki
通讯作者：
Igarashi, Yasuyuki
影响因子：
3.5
作者：
Li, DX;Gonzalez, O;Roberts, R
通讯作者：
Roberts, R
使用下一代 DNA 测序数据进行变异发现和基因分型的框架。
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
4.8
作者：
Gaigg, B;Timischl, B;Schneiter, R
通讯作者：
Schneiter, R
影响因子：
3.1
作者：
Lev, Dorit;Sadeh, Menachem;Lerman-Sagie, Tally
通讯作者：
Lerman-Sagie, Tally