Shoffner J M, Lott M T, Lezza A M, Seibel P, Ballinger S W, Wallace D C
Department of Neurology, Emory University School of Medicine, Atlanta, Georgia 30322.
Cell. 1990 Jun 15;61(6):931-7. doi: 10.1016/0092-8674(90)90059-n.
An A to G transition mutation at nucleotide pair 8344 in human mitochondrial DNA (mtDNA) has been identified as the cause of MERRF. The mutation alters the T psi C loop of the tRNA(Lys) gene and creates a CviJI restriction site, providing a simple molecular diagnostic test for the disease. This mutation was present in three independent MERRF pedigrees and absent in 75 controls, altered a conserved nucleotide, and was heteroplasmic. All MERRF patients and their less-affected maternal relatives had between 2% and 27% wild-type mtDNAs and showed an age-related association between genotype and phenotype. This suggests that a small percentage of normal mtDNAs has a large protective effect on phenotype. This mutation provides molecular confirmation that some forms of epilepsy are the result of deficiencies in mitochondrial energy production.
人类线粒体DNA（mtDNA）中第8344个核苷酸对处的A到G转换突变已被确定为肌阵挛性癫痫伴破碎红纤维病（MERRF）的病因。该突变改变了tRNA（Lys）基因的TψC环，并产生了一个CviJI限制性酶切位点，为该疾病提供了一种简单的分子诊断测试。此突变存在于三个独立的MERRF家系中，在75名对照中未出现，改变了一个保守核苷酸，且为异质性。所有MERRF患者及其受影响较小的母系亲属的野生型mtDNA含量在2%至27%之间，并显示出基因型与表型之间的年龄相关性。这表明一小部分正常的mtDNA对表型有很大的保护作用。该突变提供了分子证据，证明某些形式的癫痫是线粒体能量产生不足的结果。
