Variable clinical manifestation of homoplasmic G14459A mitochondrial DNA mutation
Variable clinical manifestation of homoplasmic G14459A mitochondrial DNA mutation
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DOI：
10.1002/ajmg.a.20456
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发表时间：
2004-02-01
影响因子：
2
通讯作者：
Wong, LJC
中科院分区：
文献类型：
--
作者：
Gropman, A;Chen, TJ;Wong, LJC
Leber遗传性视神经病变（LHON）/儿童发作性肌张力障碍与线粒体DNA（mtDNA）编码的ND 6基因内核苷酸位置（np）14459处的G至A转换相关。这种突变已在仅表现为LHON、LHON加肌张力障碍或典型发病年龄小于5岁的儿童肌张力障碍的家族中报告。该突变在氨基酸残基72处将中度保守的丙氨酸改变为缬氨酸，其在ND 6蛋白的进化上最保守的区域内。儿科发病的疾病与基底神经节功能障碍、痉挛和脑病有关。我们报告了一个线粒体基因G14459 A突变的家系，该家系具有广泛的临床表现。先证者是一名3岁女孩，有构音障碍、肌张力障碍、痉挛和轻度脑病。脑部MRI显示双侧对称基底节透亮区，伴有脑和全身性乳酸酸中毒。她的母亲堂兄弟表现为新发跛行和轻度轻偏瘫沿着相似的MRI结果，但表型要轻得多。对具有突变的家庭成员的额外调查揭示了具有线粒体疾病的可变临床和实验室特征的无症状和有症状个体。这项研究再次强调了同质性G14459 A mtDNA突变的异质性临床表现，即使在同一个家庭，并支持核基因可能在修改线粒体疾病的临床表现中发挥作用的假设。2003年出版Wiley-Liss，Inc.（匕首）。
Leber hereditary optic neuropathy (LHON)/pediatric onset dystonia is associated with a G to A transition at nucleotide position (np) 14459,within the mitochondrial DNA (mtDNA)encoded ND6 gene. This mutation has been reported in families presenting with LHON alone, LHON plus dystonia, or pediatric dystonia with typical age of onset less than 5 years. The mutation changes a moderately conserved alanine to a valine at amino acid residue 72, which is within the most evolutionarily conserved region of the ND6 protein. Pediatric onset disease is associated with basal ganglia dysfunction, spasticity, and encephalopathy. We report a family with G14459A mtDNA mutation and a broad spectrum of clinical manifestation. The proband was a 3-year-old girl with anarthria, dystonia, spasticity, and mild encephalopathy. MRI of the brain demonstrated bilateral, symmetric basal ganglia lucencies associated with cerebral and systemic lactic acidosis. Her maternal first cousin presented with a new onset limp and mild hemiparesis along with similar MRI findings with a much milder phenotype. Additional investigation of the family members with the mutation has revealed both asymptomatic and symptomatic individuals with variable clinical and laboratory features of mitochondrial disease. This study re-emphasizes the heterogeneous clinical manifestation of homoplasmic G14459A mtDNA mutation even within the same family, and supports the hypothesis that nuclear genes may play a role in modifying the clinical expression of mitochondrial disease. Published 2003 Wiley-Liss, Inc.(dagger).