Finsterer J
Krankenanstalt Rudolfstiftung, Vienna, Austria.
Acta Neurol Scand. 2007 Jul;116(1):1-14. doi: 10.1111/j.1600-0404.2007.00836.x.
Mitochondrial disorders are frequently caused by mutations in mitochondrial genes and usually present as multisystem disease. One of the most frequent mitochondrial mutations is the A3,243G transition in the tRNALeu(UUR) gene. The phenotypic expression of the mutation is variable and comprises syndromic or non-syndromic mitochondrial disorders. Among the syndromic manifestations the mitochondrial encephalopathy, lactacidosis, and stroke-like episode (MELAS) syndrome is the most frequent. In single cases the A3,243G mutation may be associated with maternally inherited diabetes and deafness syndrome, myoclonic epilepsy and ragged-red fibers (MERRF) syndrome, MELAS/MERRF overlap syndrome, maternally inherited Leigh syndrome, chronic external ophthalmoplegia, or Kearns-Sayre syndrome. The wide phenotypic variability of the mutation is explained by the peculiarities of the mitochondrial DNA, such as heteroplasmy and mitotic segregation, resulting in different mutation loads in different tissues and family members. Moreover, there is some evidence that additional mtDNA sequence variations (polymorphisms, haplotypes) influence the phenotype of the A3,243G mutation. This review aims to give an overview on the actual knowledge about the genetic, pathogenetic, and phenotypic implications of the A3,243G mtDNA mutation.
线粒体疾病通常由线粒体基因突变引起，常表现为多系统疾病。最常见的线粒体突变之一是tRNALeu(UUR)基因中的A3243G转换。该突变的表型表达具有变异性，包括综合征型或非综合征型线粒体疾病。在综合征型表现中，线粒体脑肌病、乳酸酸中毒和卒中样发作（MELAS）综合征最为常见。在个别病例中，A3243G突变可能与母系遗传的糖尿病和耳聋综合征、肌阵挛性癫痫伴破碎红纤维（MERRF）综合征、MELAS/MERRF重叠综合征、母系遗传的Leigh综合征、慢性进行性眼外肌麻痹或Kearns-Sayre综合征相关。该突变广泛的表型变异性可由线粒体DNA的特性来解释，如异质性和有丝分裂分离，这导致不同组织和家庭成员中存在不同的突变负荷。此外，有证据表明，线粒体DNA的其他序列变异（多态性、单倍型）会影响A3243G突变的表型。本综述旨在概述有关A3243G线粒体DNA突变的遗传、发病机制及表型影响的现有知识。
