The novel mitochondrial tRNAAsn gene mutation m.5709T>C produces ophthalmoparesis and respiratory impairment
The novel mitochondrial tRNAAsn gene mutation m.5709T>C produces ophthalmoparesis and respiratory impairment
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DOI：
10.1038/ejhg.2011.238
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发表时间：
2012-03-01
影响因子：
5.2
通讯作者：
Comi, Giacomo P.
中科院分区：
文献类型：
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作者：
Ronchi, Dario;Sciacco, Monica;Comi, Giacomo P.
虽然线粒体tRNA突变构成了最常见的mtDNA缺陷，但线粒体tRNA（Asn）中病理性变异的存在极为罕见。我们能够确定一种新的线粒体DNA tRNA（Asn）基因致病突变与肌病表型和以前未报告的呼吸障碍。我们的先证者是一位成年女性，有眼麻痹和呼吸障碍。她的肌肉活检显示了几个细胞色素c氧化酶阴性（考克斯-）纤维和线粒体增殖的迹象（粗糙的红色纤维）。肌源性mtDNA的序列分析显示m.5709T>C取代，影响线粒体tRNAAsn基因。限制性片段长度多态性分析的突变在分离的肌纤维表明，至少91.9%的突变的mtDNA的阈值结果在考克斯缺乏症的表型。新的表型进一步增加了由tRNAAsn基因突变引起的线粒体疾病的临床谱。European Journal of Human Genetics（2012）20，357-360; doi：10.1038/ejhg.2011.238; 2011年12月21日在线发表
Although mutations in mitochondrial tRNAs constitute the most common mtDNA defect, the presence of pathological variants in mitochondrial tRNA(Asn) is extremely rare. We were able to identify a novel mtDNA tRNA(Asn) gene pathogenic mutation associated with a myopathic phenotype and a previously unreported respiratory impairment. Our proband is an adult woman with ophthalmoparesis and respiratory impairment. Her muscle biopsy presented several cytochrome c oxidase-negative (COX-) fibres and signs of mitochondrial proliferation (ragged red fibres). Sequence analysis of the muscle-derived mtDNA revealed an m.5709T>C substitution, affecting mitochondrial tRNAAsn gene. Restriction-fragment length polymorphism analysis of the mutation in isolated muscle fibres showed that a threshold of at least 91.9% mutated mtDNA results in the COX deficiency phenotype. The new phenotype further increases the clinical spectrum of mitochondrial diseases caused by mutations in the tRNAAsn gene. European Journal of Human Genetics (2012) 20, 357-360; doi:10.1038/ejhg.2011.238; published online 21 December 2011