MERRF/MELAS overlap syndrome: a double pathogenic mutation in mitochondrial tRNA genes
MERRF/MELAS overlap syndrome: a double pathogenic mutation in mitochondrial tRNA genes
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DOI：
10.1136/jmg.2009.072058
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发表时间：
2010-10-01
影响因子：
4
通讯作者：
Sasaki, H.
中科院分区：
文献类型：
--
作者：
Nakamura, M.;Yabe, I.;Sasaki, H.
背景肌阵挛性癫痫伴破碎红纤维（MERU）和线粒体脑病、乳酸性酸中毒和卒中样发作（MELAS）是线粒体脑肌病的既定表型。线粒体tRNA（LYs）基因的m.8356T>C突变是MERRF的一种致病突变。在大多数MELAS患者中检测到线粒体tRNALeu基因中的m.3243A>G转换。虽然以前对线粒体DNA（mtDNA）双突变的分析有助于讨论其性质，目的描述一个具有上述mtDNA双点突变的家系的临床和遗传学特征，并探讨mtDNA双点突变在该家系不同临床特征中的作用。患者与方法先证者为一名23岁女性MERRF患者，携带m.8356T>线粒体tRNA基因中的C和m.3243A>G转换。结果4例患者的表型均为MERRF、MERRF/MELAS重叠综合征和无症状携带者。我们假设，这个家庭的表型的过程中开始与MERRF，其次是MELAS。该双突变在4例患者的血液中均为异质性，但在每个患者中的发生率不同，而在两例受检病例的肌肉中，m.8356T>C呈同质性，而m.3243A>G呈异质性。在该家系中未检测到其他突变。结论这是首次报道的mtDNA双点突变病例。
Background Myoclonic epilepsy with ragged-red fibres (MERU) and mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS) are established phenotypes of mitochondrial encephalomyopathy. The m.8356T>C transition in the mitochondrial tRNA(LYs) gene is a pathogenic mutations of MERRF. The m.3243A>G transition in the mitochondrial tRNALeu gene is detected in most MELAS patients. Although previous analyses of double mutations in mitochondrial DNA (mtDNA) were useful for discussing their nature, many unsolved questions remain.Objective To describe the clinical and genetic features of a family with the above mtDNA double-point mutations and discuss the role of double mtDNA mutations in diverse clinical features in the family.Patients and methods The proband was a 23-year-old woman with MERRF harbouring m.8356T>C and m.3243A>G transitions in mitochondrial tRNA genes. We assessed clinical aspects of her and those other three relatives and performed mutation analyses on their mtDNA.Results Phenotypes of the four patients were MERRF, MERRF/MELAS overlap syndrome and asymptomatic carrier. We hypothesise that the course of the phenotype of this family begins with MERRF and is followed by MELAS. This double mutation was heteroplasmic in blood of all four patients but with different rates in each patient, while m.8356T>C appeared homoplasmic and m.3243A>G was heteroplasmic in muscle of the two examined cases. No other mutations were detected in the total mtDNA sequence in this family.Conclusions This is the first reported case of a double-point mutation in mtDNA, both of which were heteroplasmic and pathogenic for the established phenotypes.