Mitochondrial haplogroup D4j specific variant m.11696G>a(MT-ND4) may increase the penetrance and expressivity of the LHON-associated m.11778G>a mutation in Chinese pedigrees
Mitochondrial haplogroup D4j specific variant m.11696G>a(MT-ND4) may increase the penetrance and expressivity of the LHON-associated m.11778G>a mutation in Chinese pedigrees
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线粒体单倍群 D4j 特异性变异 m.11696G > a(MT-ND4) 可能会增加 LHON 相关 m.11778G > 中国谱系突变的外显率和表达性
DOI：
10.3109/19401736.2015.1136304
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发表时间：
2017-01-01
影响因子：
--
通讯作者：
Guan, Min-Xin
中科院分区：
文献类型：
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作者：
Xie, Shipeng;Zhang, Juanjuan;Guan, Min-Xin
利伯氏遗传性视神经病变（LHON）是最常见的线粒体疾病之一。我们在此报告了8个携带已知线粒体11778G>A（MT-ND4）突变的汉族家庭的线粒体DNA （mtDNA）的临床、遗传和分子分析。这些家庭的77名母系亲属中有37人（26男11女）表现出不同程度和发病年龄的视神经病变。外显率为25% ~ 75%，平均为42%，视力障碍的发病年龄在10 ~ 25岁之间，平均为17岁。他们的mtDNA分子分析鉴定出属于东亚单倍群d4j的不同变体组。除了已知的m. 11778g >A突变外，m. 11696G>A（MT-ND4）突变导致异亮氨酸取代缬氨酸氨基酸位置313，该位置位于ND4的预测跨膜区域。此外，据报道，m. 11696G>A突变与LHON相关，并且在这9个中国家庭中的外显率似乎高于其他仅携带m. 11778G>A突变的中国家庭。因此，线粒体单倍群D4j特异性的m. 11696G>A突变可能与原发性lhon相关的m. 11778g >A突变协同作用，从而增加了这些中国家庭中视力丧失的外显率和表达性。
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.