Exome Sequencing Identifies MRPL3 Mutation in Mitochondrial Cardiomyopathy
Exome Sequencing Identifies MRPL3 Mutation in Mitochondrial Cardiomyopathy
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DOI：
10.1002/humu.21562
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发表时间：
2011-11-01
期刊：
影响因子：
3.9
通讯作者：
Roetig, Agnes
中科院分区：
文献类型：
--
作者：
Galmiche, Louise;Serre, Valerie;Roetig, Agnes
通过将外显子组测序与基因图谱相结合，我们在一个患有肥厚性心肌病、精神运动迟缓和多发性呼吸链缺陷的四名同胞家庭中发现了大线粒体核糖体蛋白 MRPL3 的首次突变。受影响的同胞是分别从母亲和父亲遗传的错义 MRPL3 突变 (P317R) 和大规模缺失的复合杂合子。这些突变被证明会改变核糖体组装并导致培养的皮肤成纤维细胞线粒体翻译缺陷，从而导致呼吸链的多个复合物组装异常。这一观察结果支持了以下观点：外显子组测序与遗传图谱相结合是鉴定线粒体疾病新基因的有力方法。 Hum Mutat 32: 1225-1231, 2011。(C) 2011 Wiley periodicals, Inc.
By combining exome sequencing in conjunction with genetic mapping, we have identified the first mutation in large mitochondrial ribosomal protein MRPL3 in a family of four sibs with hypertrophic cardiomyopathy, psychomotor retardation, and multiple respiratory chain deficiency. Affected sibs were compound heterozygotes for a missense MRPL3 mutation (P317R) and a large-scale deletion, inherited from the mother and the father, respectively. These mutations were shown to alter ribosome assembly and cause a mitochondrial translation deficiency in cultured skin fibroblasts resulting in an abnormal assembly of several complexes of the respiratory chain. This observation gives support to the view that exome sequencing combined with genetic mapping is a powerful approach for the identification of new genes of mitochondrial disorders. Hum Mutat 32: 1225-1231, 2011. (C) 2011 Wiley Periodicals, Inc.