Variable phenotypes in a family with mitochondrial encephalomyopathy harboring a 3291T > C mutation in mitochondrial DNA
Variable phenotypes in a family with mitochondrial encephalomyopathy harboring a 3291T > C mutation in mitochondrial DNA
复制标题
DOI：
10.1007/s10072-011-0719-9
复制
发表时间：
2011-10-01
影响因子：
3.3
通讯作者：
Matsubara, Shiro
中科院分区：
文献类型：
--
作者：
Sunami, Yoko;Sugaya, Keizo;Matsubara, Shiro
我们报告一个日本家系，患有线粒体DNA(MtDNA)3291位核苷酸的T-C转换相关的线粒体脑肌病。临床表现为小脑性共济失调伴肌病、反复头痛、肌阵挛和癫痫。单个家系中受影响成员的表型变异和突变分析表明母体遗传是异质性的，这与公认的与mtDNA tRNA基因的许多致病点突变有关的现象是一致的。3291突变是一种罕见的mtDNA突变，其临床表现仅在3例散发病例中报道。这是分离出3291突变并伴有多代母系复发性线粒体脑病的家庭的第一份报告。我们的发现为线粒体DNA中3291T和GT；C突变的致病性及其特有的临床异质性提供了确凿的证据。
We present a Japanese family suffering from mitochondrial encephalomyopathy associated with a T-to-C transition at mitochondrial DNA (mtDNA) nucleotide position 3291. Clinical manifestations of the patients include cerebellar ataxia with myopathy, recurrent headache, and myoclonus and epilepsy. The phenotypic variation among the affected members of a single family and the mutational analysis showing maternal inheritance in a heteroplasmic fashion are consistent with well-recognized phenomena associated with many pathogenic point mutations of mtDNA tRNA genes. The 3291 mutation is a rare mtDNA mutation whose clinical presentation had only been reported in three sporadic cases. This is the first report of a family segregating the 3291 mutation with multigenerational matrilinear recurrence of mitochondrial encephalopathy. Our findings provide conclusive evidence for the pathogenicity of the 3291T > C mutation in mtDNA and its characteristic clinical heterogeneity.