Department of Neurology, Peking University First Hospital, Beijing, China.
J Hum Genet. 2011 Nov;56(11):759-64. doi: 10.1038/jhg.2011.96. Epub 2011 Aug 18.
The mutation pattern of mitochondrial DNA (mtDNA) in mainland Chinese patients with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) has been rarely reported, though previous data suggested that the mutation pattern of MELAS could be different among geographically localized populations. We presented the results of comprehensive mtDNA mutation analysis in 92 unrelated Chinese patients with MELAS (85 with classic MELAS and 7 with MELAS/Leigh syndrome (LS) overlap syndrome). The mtDNA A3243G mutation was the most common causal genotype in this patient group (79/92 and 85.9%). The second common gene mutation was G13513A (7/92 and 7.6%). Additionally, we identified T10191C (p.S45P) in ND3, A11470C (p. K237N) in ND4, T13046C (p.M237T) in ND5 and a large-scale deletion (13025-13033:14417-14425) involving partial ND5 and ND6 subunits of complex I in one patient each. Among them, A11470C, T13046C and the single deletion were novel mutations. In summary, patients with mutations affecting mitochondrially encoded complex I (MTND) reached 12.0% (11/92) in this group. It is noteworthy that all seven patients with MELAS/LS overlap syndrome were associated with MTND mutations. Our data emphasize the important role of MTND mutations in the pathogenicity of MELAS, especially MELAS/LS overlap syndrome.
中国大陆线粒体肌病、脑肌病、乳酸酸中毒和卒中样发作(MELAS)患者中线粒体 DNA(mtDNA)的突变模式鲜有报道,尽管先前的数据表明 MELAS 的突变模式可能因地理位置不同而存在差异。我们报告了 92 例 MELAS 患者(85 例经典 MELAS 和 7 例 MELAS/ Leigh 综合征重叠综合征)的全面 mtDNA 突变分析结果。该患者组中最常见的致病基因型是 mtDNA A3243G 突变(79/92 和 85.9%)。第二种常见的基因突变是 G13513A(7/92 和 7.6%)。此外,我们还在 ND3 中发现了 T10191C(p.S45P)、ND4 中的 A11470C(p.K237N)、ND5 中的 T13046C(p.M237T)以及 1 例患者中涉及部分 ND5 和 ND6 亚基的大片段缺失(13025-13033:14417-14425)。其中,A11470C、T13046C 和单个缺失是新发现的突变。综上所述,该组患者中影响线粒体编码复合物 I(MTND)的突变患者达到 12.0%(11/92)。值得注意的是,7 例 MELAS/Leigh 综合征重叠综合征患者均与 MTND 突变相关。我们的数据强调了 MTND 突变在线粒体肌病、尤其是 MELAS/Leigh 综合征重叠综合征发病机制中的重要作用。