线粒体DNA 8344A>G突变导致线粒体遗传病的研究进展和防治策略

doi:10.12280/gjszjk.20230358

摘要/Abstract

摘要：

线粒体DNA（mitochondrial DNA，mtDNA）突变会导致以呼吸链受损为特征的一系列线粒体疾病，这类疾病以发病早、难治愈、母系遗传为特点。线粒体tRNA赖氨酸基因中第8 344位点的突变会导致mtDNA编码蛋白的翻译减少，机体能量供应不足，导致肌阵挛性癫痫伴破碎红纤维（myoclonic epilepsy associated with ragged red fiber，MERRF）综合征，产生严重的肌阵挛、癫痫发作、共济失调等症状，另一种特征性病变是颈后及上背部多发对称性脂肪瘤病（multiple symmetric lipomatosis，MSL）。在所有致病性mtDNA突变中，m.8344A>G突变约占4%；核基因修饰和环境因素可能共同参与了m.8344A>G突变的致病过程。目前MERRF综合征缺乏特定的治疗方式。基于辅助生殖技术的胚胎植入前遗传学诊断和线粒体置换技术有望成为治疗此类线粒体遗传病的新方法，但其安全性和有效性仍需进一步验证。

关键词: DNA，线粒体, 基因，线粒体, 突变, 线粒体疾病, MERRF综合征, 植入前诊断, 线粒体置换

Abstract:

Mutations in mitochondrial DNA (mtDNA) may lead to a range of mitochondrial diseases that are related to the damage of the mitochondrial respiratory chain. These mitochondrial diseases are characterized by early onset, difficult-to-cure and maternal inheritance. Mutations at site 8 344 in the mitochondrial tRNA lysine gene can result in the reduced translation of the protein encoded by mtDNA and an inadequate energy supply, leading to myoclonic epilepsy associated with ragged red fiber (MERRF) syndrome, with severe myoclonic symptoms, seizures and ataxia. Another characteristic lesion is multiple symmetric lipomatosis (MSL) in the posterior neck and upper back. Among all of pathogenic mtDNA mutations, m.8344A>G mutations were accounted for about 4%. Nuclear gene modification and environmental factors may be involved in the pathogenesis of m.8344A>G mutation. At present, the specific treatment methods for MERRF are lacking. Preimplantation genetic diagnosis and mitochondrial transplantation based on assisted reproductive technology are expected to be new methods for the treatment of this kind of mitochondrial genetic diseases, but the safety and effectiveness still need to be further verified.

Key words: DNA, mitochondrial, Genes, mitochondrial, Mutation, Mitochondrial diseases, MERRF syndrome, Preimplantation diagnosis, Mitochondrial replacement

沈凌超, 王鑫, 纪冬梅. 线粒体DNA 8344A>G突变导致线粒体遗传病的研究进展和防治策略[J]. 国际生殖健康/计划生育杂志, 2023, 42(6): 471-475.

SHEN Ling-chao, WANG Xin, JI Dong-mei. Advances and Prevention Strategies for Mitochondrial Genetic Diseases Caused by the Mitochondrial DNA 8344A>G Mutation[J]. Journal of International Reproductive Health/Family Planning, 2023, 42(6): 471-475.

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