Diagnosis of mitochondrial disorders by concomitant next-generation sequencing of the exome and mitochondrial genome.
Diagnosis of mitochondrial disorders by concomitant next-generation sequencing of the exome and mitochondrial genome.
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DOI：
10.1016/j.ygeno.2013.04.013
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发表时间：
2013-09
期刊：
影响因子：
4.4
通讯作者：
Kingsmore SF
中科院分区：
文献类型：
--
作者：
Dinwiddie DL;Smith LD;Miller NA;Atherton AM;Farrow EG;Strenk ME;Soden SE;Saunders CJ;Kingsmore SF
线粒体疾病是出了名的难以诊断，由于极端的基因座和等位基因异质性，核和线粒体基因组都有可能患病。使用外显子组测序，我们展示了快速和成本有效地评估核和线粒体基因组的能力，以获得四名患有三种不同线粒体疾病的患者的分子诊断。1例患者因MT-ATP6突变而被发现患有Leigh综合征，2例受影响的兄弟姐妹因NDUFV1基因突变而被发现为复合杂合，导致线粒体复合物I缺陷，1例患者因COQ2复合杂合突变而被发现患有辅酶Q10缺陷。在所有病例中，传统的诊断测试都未能确定分子诊断。我们建议进行更多的研究来评估外显子组测序作为线粒体疾病的主要诊断测试，包括mtDNA突变引起的疾病。
Mitochondrial diseases are notoriously difficult to diagnose due to extreme locus and allelic heterogeneity, with both nuclear and mitochondrial genomes potentially liable. Using exome sequencing we demonstrate the ability to rapidly and cost effectively evaluate both the nuclear and mitochondrial genomes to obtain a molecular diagnosis for four patients with three distinct mitochondrial disorders. One patient was found to have Leigh syndrome due to a mutation in MT-ATP6, two affected siblings were discovered to be compound heterozygous for mutations in the NDUFV1 gene, which causes mitochondrial complex I deficiency, and one patient was found to have coenzyme Q10 deficiency due to compound heterozygous mutations in COQ2. In all cases conventional diagnostic testing failed to identify a molecular diagnosis. We suggest that additional studies should be conducted to evaluate exome sequencing as a primary diagnostic test for mitochondrial diseases, including those due to mtDNA mutations.