A variant of Leber hereditary optic neuropathy characterized by recovery of vision and by an unusual mitochondrial genetic etiology.
A variant of Leber hereditary optic neuropathy characterized by recovery of vision and by an unusual mitochondrial genetic etiology.
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DOI：
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发表时间：
1992-12
影响因子：
9.8
通讯作者：
D. Mackey;N. Howell
中科院分区：
文献类型：
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作者：
D. Mackey;N. Howell
Tas 2和Vic 2澳大利亚家族受到Leber遗传性视神经病变（LHON）变体的影响。发生视神经病变的风险显示严格的母系遗传，受影响的家庭成员的眼科变化是LHON的特征。然而，与这种疾病的常见形式相反，这两个家族的成员表现出很高的视力恢复频率。为了确定这些家族中LHON的线粒体遗传病因，测定了两个家族代表的（a）编码线粒体链复合物I亚基的7个线粒体基因的核苷酸序列和（B）线粒体细胞色素B基因。两个家族都没有携带任何先前鉴定的主要线粒体LHON突变：ND 4/11778，ND 1/3460或ND 1/4160。相反，两个LHON家族在线粒体复合物I基因中携带多个核苷酸变化，这产生保守的氨基酸变化。从可用的序列数据，可以推断，Vic 2和Tas 2 LHON家族在遗传学上彼此相关，并且与一组LHON家族相关，其中线粒体细胞色素B基因中的突变被假设起主要病因作用。然而，测序分析确定Vic 2和Tas 2 LHON家族不携带这些细胞色素B突变。有两种假设来解释Tas 2和Vic 2 LHON家族中LHON的不寻常的线粒体遗传病因。一种可能性是在线粒体基因组内存在主要LHON突变，但其位于未包括在测序分析中的位点。或者，这些家族中的疾病可能是由多个继发性LHON突变的累积效应引起的，这些突变具有不太严重的表型后果。
The Tas2 and Vic2 Australian families are affected with a variant of Leber hereditary optic neuropathy (LHON). The risk of developing the optic neuropathy shows strict maternal inheritance, and the ophthalmological changes in affected family members are characteristic of LHON. However, in contrast to the common form of the disease, members of these two families show a high frequency of vision recovery. To ascertain the mitochondrial genetic etiology of the LHON in these families, both (a) the the nucleotide sequences of the seven mitochondrial genes encoding subunits of respiratory-chain complex I and (b) the mitochondrial cytochrome b gene were determined for representatives of both families. Neither family carries any of the previously identified primary mitochondrial LHON mutations: ND4/11778, ND1/3460, or ND1/4160. Instead, both LHON families carry multiple nucleotide changes in the mitochondrial complex I genes, which produce conservative amino acid changes. From the available sequence data, it is inferred that the Vic2 and Tas2 LHON families are phylogenetically related to each other and to a cluster of LHON families in which mutations in the mitochondrial cytochrome b gene have been hypothesized to play a primary etiological role. However, sequencing analysis establishes that the Vic2 and Tas2 LHON families do not carry these cytochrome b mutations. There are two hypotheses to account for the unusual mitochondrial genetic etiology of the LHON in the Tas2 and Vic2 LHON families. One possibility is that there is a primary LHON mutation within the mitochondrial genome but that it is at a site that was not included in the sequencing analyses. Alternatively, the disease in these families may result from the cumulative effects of multiple secondary LHON mutations that have less severe phenotypic consequences.