Mutation in the mitochondrial translation elongation factor EFTs results in severe infantile liver failure
Mutation in the mitochondrial translation elongation factor EFTs results in severe infantile liver failure
复制标题
DOI：
10.1016/j.jhep.2011.06.014
复制
发表时间：
2012-01-01
影响因子：
25.7
通讯作者：
Roetig, Agnes
中科院分区：
文献类型：
--
作者：
Vedrenne, Vanessa;Galmiche, Louise;Roetig, Agnes
背景与目的：多条呼吸链缺陷是线粒体疾病的常见原因，常导致肝功能衰竭。相当一部分患者出现线粒体DNA枯竭，但仍有一些病例无法解释。本研究的目的是确定一个胎儿宫内发育迟缓、新生儿乳酸中毒、肝功能障碍和肌肉多呼吸链缺陷的家系的致病基因。方法：采用50K SNP基因分型方法进行纯合子定位，并对该家系成员的基因组DNA进行直接测序分析候选基因。结果：SNP基因分型检测到多个纯合子区域，重点关注参与线粒体翻译的基因。我们对编码线粒体翻译因子EFTs的TSFM基因进行了测序，发现了一个将高度保守的精氨酸转变为色氨酸的纯合子突变(R312W)。结论：该突变以前在两个不相关的家系中被报道过，表现为两个不同的综合征(分别是致命性线粒体脑肌病和肥厚性心肌病)。与相同的TSFM突变相关的第三种综合征的描述支持了人类线粒体翻译缺陷的广泛的临床和遗传异质性。提示线粒体翻译缺陷是婴幼儿线粒体来源的肝功能衰竭的一个日益严重的原因。(C)2011年欧洲肝脏研究协会。爱思唯尔出版，版权所有。
Background & Aims: Multiple respiratory chain deficiencies represent a common cause of mitochondrial diseases and often result in hepatic failure. A significant fraction of patients present mitochondrial DNA depletion but a number of cases remain unexplained. The aim of our study was to identify the disease causing gene in a kindred with intrauterine growth retardation, neonatal lactic acidosis, liver dysfunction and multiple respiratory chain deficiency in muscle.Methods: Homozygosity mapping was performed by 50K SNP genotyping and candidate genes were successively analyzed by direct sequencing on genomic DNA of the family members.Results: SNP genotyping detected several regions of homozygosity in which we focused our attention to genes involved in mitochondrial translation. We sequenced the TSFM gene, encoding the mitochondrial translation factor EFTs and identified a homozygous mutation changing a highly conserved arginine into a tryptophan (R312W).Conclusions: This mutation has been previously reported in two unrelated kindred presenting two distinct syndromes (fatal mitochondrial encephalomyopathy and hypertrophic cardiomyopathy respectively). The description of a third syndrome associated with a same TSFM mutation gives support to the broad clinical and genetic heterogeneity of mitochondrial translation deficiencies in human. It suggests that mitochondrial translation deficiency represents a growing cause of hepatic failure of mitochondrial origin in infants. (C) 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.