Confirmation of the mitochondrial ND1 gene mutation G3635A as a primary LHON mutation
Confirmation of the mitochondrial ND1 gene mutation G3635A as a primary LHON mutation
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确认线粒体 ND1 基因突变 G3635A 为原发性 LHON 突变
DOI：
10.1016/j.bbrc.2009.05.127
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发表时间：
2009-08-14
影响因子：
3.1
通讯作者：
Ma, Xu
中科院分区：
文献类型：
--
作者：
Yang, Juhua;Zhu, Yihua;Ma, Xu
我们报告了两个不携带原发性LHON突变的中国LHON家族的临床和遗传特征。线粒体基因组序列分析显示，在这两个家庭的同质ND 1 G3635 A突变的存在。在家族LHON-001中，鉴定了属于东亚单倍群R11 a的31个其他变体，在家族LHON-019中，确定了属于东亚单倍群D4 g的37个其他变体。ND 1 G3635 A突变将转换的丝氨酸（110）残基改变为天冬酰胺。这种突变先前已在单个俄罗斯LHON家族中描述，并被认为有助于增加LHON表达。此外，细胞色素c氧化酶亚基II的C7868 T突变（COII/L95 F）可能与G3635 A协同作用，增加家族LHON-001中的LHON表达率，该家族的LHON外显率水平高于家族LHON-019。总之，G3635 A突变被证实为LHON的罕见原发性致病突变。(C)2009 Elsevier Inc. All rights reserved.
We report the clinical and genetic characterization of two Chinese LHON families who do not carry the primary LHON-mutations. Mitochondrial genome sequence analysis revealed the presence of a homoplasmic ND1 G3635A mutation in both families. In Family LHON-001, 31 other variants belonging to the East Asian haplogroup R11a were identified and in Family LHON-019, 37 other variants belonging to the East Asian haplogroup D4g were determined. The ND1 G3635A mutation changes the conversed serine(110) residue to asparagine. This mutation has been previously described in a single Russian LHON family and has been suggested to contribute to increased LHON expressivity. In addition, a mutation in cytochrome c oxidase subunit II at C7868T (COII/L95F) may act in synergy with G3635A, increasing LHON expressivity in Family LHON-001, which had a higher level of LHON penetrance than Family LHON-019. In summary, the G3635A mutation is confirmed as a rare primary pathogenic mutation for LHON. (C) 2009 Elsevier Inc. All rights reserved.