Mutant NDUFV2 subunit of mitochondrial complex I causes early onset hypertrophlic cardiomyopathy and encephalopathy
Mutant NDUFV2 subunit of mitochondrial complex I causes early onset hypertrophlic cardiomyopathy and encephalopathy
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DOI：
10.1002/humu.10225
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发表时间：
2003-06-01
期刊：
影响因子：
3.9
通讯作者：
Munnich, A
中科院分区：
文献类型：
--
作者：
Bénit, P;Beugnot, R;Munnich, A
呼吸链复合物I缺陷代表了由线粒体或核DNA突变引起的一组遗传异质性疾病。结合变性高效液相色谱和序列分析，我们发现NDUFV 2基因（编码NADH脱氢酶泛醌黄素蛋白2）内含子2（IVS 2 +5_+8delGTAA）的一个4-bp缺失导致一个近亲家系的三个患病同胞的复合物I缺陷和早发性肥厚型心肌病伴躯干肌张力减退。纯合突变改变了外显子2的共有剪接供体位点，导致NDUFV 2蛋白和复合物I缺陷减少70%。虽然编码复合物I亚基的许多基因的突变基本上导致神经症状，但NDUFV 2中的第一个突变与心肌病显著相关，如先前在NDFUS 2突变的独特病例中观察到的那样。(C)2003 Wiley-Liss，Inc.
Respiratory chain complex I deficiencies represent a genetically heterogeneous group of diseases resulting from mutations in either mitochondrial or nuclear DNA. Combination of denaturing high performance liquid chromatography and sequence analysis allowed us to show that a 4-bp deletion in intron 2 (IVS2+5_+8delGTAA) of the NDUFV2 gene (encoding NADH dehydrogenase ubiquinone flavoprotein 2) causes complex I deficiency and early onset hypertrophic cardiomyopathy with trunk hypotonia in three affected sibs of a consanguineous family. The homozygous mutation altering the consensus splice-donor site of exon 2 resulted in 70% decreased NDUFV2 protein and complex I deficiency. While mutation in a number of genes encoding complex I subunits essentially result in neurological symptoms, this first mutation in NDUFV2 is strikingly associated with cardiomyopathy, as previously observed in the unique case of NDFUS2 mutations. (C) 2003 Wiley-Liss, Inc.