Department of Neurology, Oulu University Hospital, P.O. Box 20, Oulu FI-90029, OYS, Finland.
BMC Med Genet. 2013 Jul 19;14:73. doi: 10.1186/1471-2350-14-73.
Mitochondrial diseases caused by mutations in mitochondrial DNA (mtDNA) affect tissues with high energy demand. Epilepsy is one of the manifestations of mitochondrial dysfunction when the brain is affected. We have studied here 79 Finnish patients with epilepsy and who have maternal first- or second-degree relatives with epilepsy, sensorineural hearing impairment or diabetes mellitus.
The entire mtDNA was studied by using conformation sensitive gel electrophoresis and PCR fragments that differed in mobility were directly sequenced.
We found a common nonsynonymous variant m.15218A > G (p.T158A, MTCYB) that occurs in haplogroup U5a1 to be more frequent in patients with epilepsy. The m.15218A > G variant was present in five patients with epilepsy and in four out of 403 population controls (p = 0.0077). This variant was present in two branches in the phylogenetic network constructed on the basis of mtDNA variation among the patients. Three algorithms predicted that m.15218A > G is damaging in effect.
We suggest that the m.15218A > G variant is mildly deleterious and that mtDNA involvement should be considered in patients with epilepsy and who have a maternal history of epilepsy, sensorineural hearing impairment or diabetes mellitus.
由线粒体 DNA（mtDNA）突变引起的线粒体疾病会影响高能量需求的组织。当大脑受到影响时，癫痫是线粒体功能障碍的表现之一。我们在此研究了 79 名芬兰癫痫患者，他们的母亲一级或二级亲属有癫痫、感觉神经性听力障碍或糖尿病。
使用构象敏感凝胶电泳研究整个 mtDNA，直接对移动性不同的 PCR 片段进行测序。
我们发现一个常见的非同义突变 m.15218A>G（p.T158A，MTCYB）在母系 haplogroup U5a1 中更为频繁，发生在癫痫患者中。该 m.15218A>G 变体存在于五名癫痫患者和 403 名人群对照中的四名中（p=0.0077）。该变体存在于基于患者之间 mtDNA 变异构建的系统发育网络中的两个分支中。三种算法预测 m.15218A>G 具有破坏性影响。
我们建议 m.15218A>G 变体具有轻度的有害性，并且应考虑在患有癫痫且有母系癫痫、感觉神经性听力障碍或糖尿病病史的患者中涉及 mtDNA。
