Mitochondrial variants may influence the phenotypic manifestation of Leber's hereditary optic neuropathy-associated ND4 G11778A mutation
Mitochondrial variants may influence the phenotypic manifestation of Leber's hereditary optic neuropathy-associated ND4 G11778A mutation
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DOI：
10.1016/s1673-8527(08)60086-7
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发表时间：
2008-11-01
影响因子：
5.9
通讯作者：
Guan, Min-Xin
中科院分区：
文献类型：
--
作者：
Cai, Wanshi;Fu, Qun;Guan, Min-Xin
我们在这里报告的特点，一个五代汉族家庭与Leber的遗传性视神经病变（LHON）。引人注目的是，这个中国家庭表现出高度的视觉丧失的模糊性和表现力。在这个家庭中，视力丧失的平均发病年龄为18岁。该家族29名母系亲属中有19名（11名男性/8名女性）出现视力丧失，严重程度从失明到正常视力不等。该家系线粒体基因组序列分析显示存在ND 4 G11778 A突变和属于亚洲单倍群M7 b的44个其他变体。G11778 A突变存在于该中国家庭的母系亲属的同源性。在其他变异体中，CO 1 G6480 A、ND 5 T12811 C和Cytb A15395 G位于相应多肽的高度保守残基。事实上，这些变异与其他临床异常有关。在这里，这些变体可能与主要的LHON相关的G11778 A突变协同作用。因此，由主要ND 4 G11778 A突变引起的线粒体功能障碍可能会因这些线粒体变体而恶化。结果提示，G6480 A、T12811 C和A15395 G变异体可能在该中国家系中具有增加原发性LHON相关G11778 A突变的表达率和表达率的潜在修饰作用。
We report here the characterization of a five-generation Han Chinese family with Leber's hereditary optic neuropathy (LHON). Strikingly, this Chinese family displayed high penetrance and expressivity of visual loss. The average age-of-onset of vision loss was 18 years in this family. Nineteen (11 males/8 females) of 29 matrilineal relatives in this family developed visual loss with a wide range of severity, ranging from blindness to normal vision. Sequence analysis of mitochondrial genome in this pedigree revealed the presence of the ND4 G11778A mutation and 44 other variants belonging to Asian haplogroup M7b. The G11778A mutation is present at homoplasmy in matrilineal relatives of this Chinese family. Of other variants, the CO1 G6480A, ND5 T12811 C and Cytb A15395G located at highly conserved residues of corresponding polypeptides. In fact, these variants were implicated to be involved in other clinical abnormalities. Here, these variants may act in synergy with the primary LHON-associated G11778A mutation. Thus, the mitochondrial dysfunction caused by the primary ND4 G11778A mutation may be worsened by these mitochondrial variants. The results imply that the G6480A, T 12811 C and A15395G variants might have a potential modifier role in increasing the penetrance and expressivity of the primary LHON-associated G11778A mutation in this Chinese family.