Deleterious mutation in the mitochondrial arginyl-transfer RNA synthetase gene is associated with pontocerebellar hypoplasia
Deleterious mutation in the mitochondrial arginyl-transfer RNA synthetase gene is associated with pontocerebellar hypoplasia
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DOI：
10.1086/521227
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发表时间：
2007-10-01
影响因子：
9.8
通讯作者：
Elpeleg, Orly
中科院分区：
文献类型：
--
作者：
Edvardson, Simon;Shaag, Avraham;Elpeleg, Orly
在一个近亲西班牙系犹太家庭中进行了纯合子定位，其中有三名患者表现出严重的婴儿脑病，伴有桥脑小脑发育不全和多线粒体呼吸链缺陷。这导致在RARS2（编码线粒体精氨酸转移RNA （tRNA）合成酶的基因）中发现一个内含子突变。该突变与患者成纤维细胞中异常短的RARS2转录物的产生和线粒体tRNA（Arg）转录物的显著减少有关。我们推测，线粒体氨酰基1- trna合成酶基因的错误剪接突变优先影响大脑，因为剪接机制具有组织特异性的脆弱性。
Homozygosity mapping was performed in a consanguineous Sephardic Jewish family with three patients who presented with severe infantile encephalopathy associated with pontocerebellar hypoplasia and multiple mitochondrial respiratory-chain defects. This resulted in the identification of an intronic mutation in RARS2, the gene encoding mitochondrial arginine-transfer RNA (tRNA) synthetase. The mutation was associated with the production of an abnormally short RARS2 transcript and a marked reduction of the mitochondrial tRNA(Arg) transcript in the patients' fibroblasts. We speculate that missplicing mutations in mitochondrial aminoacy1-tRNA synthethase genes preferentially affect the brain because of a tissue-specific vulnerability of the splicing machinery.