Xie Shipeng, Zhang Juanjuan, Sun Jiji, Zhang Minglian, Zhao Fuxin, Wei Qi-Ping, Tong Yi, Liu Xiaoling, Zhou Xiangtian, Jiang Pingping, Ji Yanchun, Guan Min-Xin
a Department of Ophthalmology , Xingtai Eye Hospital , Xingtai , Hebei , China.
b Institute of Genetics , Zhejiang University School of Medicine , Hangzhou , Zhejiang , China.
Mitochondrial DNA A DNA Mapp Seq Anal. 2017 May;28(3):434-441. doi: 10.3109/19401736.2015.1136304. Epub 2016 Jan 22.
Leber's hereditary optic neuropathy (LHON) is one of the most common mitochondrial disorders. We report here the clinical, genetic and molecular analysis of mitochondrial DNA (mtDNA) in eight Han Chinese families carrying the known mitochondrial 11778G > A(MT-ND4) mutation. Thirty-seven (26 males/11 females) of 77 matrilineal relatives in these families exhibited the variable severity and age-at-onset of optic neuropathy. The penetrances were from 25% to 75%, with the average of 42%, and the age-at-onset for visual impairment varied from 10 to 25 years, with the average of 17 in these Chinese pedigrees. Molecular analysis of their mtDNA identified distinct sets of variants belonging to the Eastern Asian haplogroupD4j. Except the known m.11778G > A mutation, the m.11696G > A(MT-ND4) mutation caused the substitution of an isoleucine for valineat amino acid position 313, located in a predicted transmembrane region of ND4. And, it is reported that the m.11696G > A mutation was associated with LHON, and appeared to contribute to higher penetrance in these nine Chinese families than other Chinese families carrying only the m.11778G > A mutation. Therefore, the mitochondrial haplogroup D4j specific m.11696G > A mutation may act in synergy with the primary LHON-associated m.11778G > A mutation, thereby increasing the penetrance and expressivity of visual loss in these Chinese families.
Leber遗传性视神经病变（LHON）是最常见的线粒体疾病之一。我们在此报告对8个携带已知线粒体11778G＞A（MT-ND4）突变的汉族家系中线粒体DNA（mtDNA）的临床、遗传和分子分析。这些家系中77名母系亲属中的37名（26名男性/11名女性）表现出视神经病变严重程度和发病年龄的差异。外显率为25%至75%，平均为42%，这些中国家系中视力损害的发病年龄在10至25岁之间，平均为17岁。对其mtDNA的分子分析确定了属于东亚单倍群D4j的不同变异组。除了已知的m.11778G＞A突变外，m.11696G＞A（MT-ND4）突变导致位于ND4预测跨膜区域的第313位氨基酸处缬氨酸被异亮氨酸取代。并且，据报道m.11696G＞A突变与LHON相关，在这九个中国家系中似乎比仅携带m.11778G＞A突变的其他中国家系具有更高的外显率。因此，线粒体单倍群D4j特异性的m.11696G＞A突变可能与主要的LHON相关m.11778G＞A突变协同作用，从而增加这些中国家系中视力丧失的外显率和表现度。
