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目的报道2例携带MT-ND6基因突变的线粒体病患者的临床和分子遗传学特点,探究线粒体DNA突变的致病机制。方法详细收集患者的临床资料,排除常见线粒体病突变位点(如A3243G,A8344G,T8993G/C,G13513A等)后,应用聚合酶链式反应-直接测序法分析16.6kb的线粒体基因组全序列,并应用Mito Tool在线软件进行氨基酸序列保守性分析,PROVEAN、SIFT和Poly Phen-2等软件进行错义突变的功能分析并判定突变性质。结果 2名先证者在ND6基因上各发现1个mt DNA变异,分别为G14453A和T14325C,二者均位于基因保守区,预测显示对蛋白功能有害,父母及100名健康对照中均未发现上述突变。结论 G14453A是MT-ND6基因上罕见的致病突变位点,该突变与MELAS综合征的发生密切相关;T14325C是LHON的可疑致病位点,但其致病性有待进一步研究。线粒体基因全测序不仅有助于常见线粒体病的临床诊断和产前筛查,还能提高一些临床表现不典型的线粒体病的分子诊断水平。
Objective To report the clinical and molecular genetic features of 2 patients with mitochondrial DNA mutations carrying MT-ND6 gene and to explore the pathogenesis of mitochondrial DNA mutations. Methods The clinical data of patients were collected in detail. Excluding the common mitochondrial mutation sites (such as A3243G, A8344G, T8993G / C and G13513A), the 16.6kb mitochondrial genome was analyzed by polymerase chain reaction-direct sequencing Amino acid sequence analysis using Mito Tool online software, software such as PROVEAN, SIFT and Poly Phen-2 were used to analyze the function of missense mutation and determine the nature of mutation. Results Two probands found one mt DNA mutation in each ND6 gene, namely G14453A and T14325C, respectively. Both of them were located in the conserved region of the gene and the prediction showed that they were detrimental to protein function. None of the parents and 100 healthy controls found the above mutation. Conclusion G14453A is a rare disease-causing mutation in MT-ND6 gene. This mutation is closely related to the occurrence of MELAS syndrome. T14325C is a suspicious pathogenic site of LHON, but its pathogenicity needs further study. Mitochondrial gene sequencing not only contributes to the clinical diagnosis and prenatal screening of common mitochondrial diseases, but also improves the molecular diagnosis of some mitochondrial diseases with atypical clinical manifestations.