The mitochondrial tRNAThr A15951G mutation may influence the phenotypic expression of the LHON-associated ND4 G1 1778A mutation in a Chinese family
The mitochondrial tRNAThr A15951G mutation may influence the phenotypic expression of the LHON-associated ND4 G1 1778A mutation in a Chinese family
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DOI：
10.1016/j.gene.2006.02.014
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发表时间：
2006-07-05
期刊：
影响因子：
3.5
通讯作者：
Guan, Min-Xin
中科院分区：
文献类型：
--
作者：
Ronghua, Li;Qu, Jia;Guan, Min-Xin
我们在这里报告的特点，一个三代汉族家庭与Leber的遗传性视神经病变（LHON）。这个中国家庭表现出高度的视力障碍的隐蔽性和表达性。平均发病年龄为19岁。在这个中国家庭中，所有的配偶和33%的女性母系亲属都发生了视力丧失，严重程度从失明到正常视力不等。该家系完整线粒体DNA的序列分析显示存在ND4 G11778A突变和40个其他变异，属于亚洲单倍群D4。G11778A突变存在于该中国家庭的母系亲属的同源性。在其他变体中，同质A15951G突变是特别感兴趣的，因为它位于邻近3'端，在tRNA（Thr）的常规位置71处。从细菌到人类线粒体高度保守的tRNAThr这个位置上的腺嘌呤（A71）对tRNA身份和前tRNA加工非常重要。事实上，在携带A15951G和G11778A突变的细胞中观察到tRNA（Thr）稳态水平的显著降低，但在仅携带G11778A突变的细胞中没有观察到。因此，A15951G突变最有可能导致线粒体tRNA代谢失败，使与原发性G11778A突变相关的线粒体功能障碍恶化。提示tRNAThr A15951G突变可能对该家系LHON相关的G11778A突变的表达率和表达率有潜在的调节作用。(c)2006 Elsevier B.V.保留所有权利。
We report here the characterization of a three-generation Han Chinese family with Leber's hereditary optic neuropathy (LHON). This Chinese family exhibited high penetrance and expressivity of visual impairment. The average age-of-onset was 19 years in this family. All mate and 33% female matrilineal relatives in this Chinese family developed visual loss with a wide range of severity, ranging from blindness to normal vision. Sequence analysis of the complete mitochondrial DNA in this pedigree revealed the presence of the ND4 G11778A mutation and 40 other variants, belonging to the Asian haplogroup D4. The G11778A mutation is present at homoplasmy in matrilineal relatives of this Chinese family. Of other variants, the homoplasmic A15951G mutation is of special interest as it is located adjacent to 3' end, at conventional position 71 of tRNA(Thr). The adenine (A71) at this position of tRNAThr, highly conserved from bacteria to human mitochondria, has been implicated to be important for tRNA identity and pre-tRNA processing. In fact, the significant reduction of the steady-state levels in tRNA(Thr), was observed in cells carrying both the A15951G and G11778A mutations but not cells carrying only G11778A mutation. Thus, the A15951G mutation most probably leads to a failure in mitochondrial tRNA metabolism, worsening the mitochondrial dysfunction associated with the primary G11778A mutation. These imply that the tRNAThr A15951G mutation may have a potential modifier role in increasing the penetrance and expressivity of the primary LHON-associated G11778A mutation in this Chinese family. (c) 2006 Elsevier B.V. All rights reserved.