MPV17 Mutations Causing Adult-Onset Multisystemic Disorder With Multiple Mitochondrial DNA Deletions.

Caterina Garone, Juan Carlos Rubio, Sarah E Calvo, Ali Naini, Kurenai Tanji, Salvatore Dimauro, Vamsi K Mootha, Michio Hirano
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引用次数: 69

Abstract

OBJECTIVE To identify the cause of an adult-onset multisystemic disease with multiple deletions of mitochondrial DNA (mtDNA). DESIGN Case report. SETTING University hospitals. PATIENT A 65-year-old man with axonal sensorimotor peripheral neuropathy, ptosis, ophthalmoparesis, diabetes mellitus, exercise intolerance, steatohepatopathy, depression, parkinsonism, and gastrointestinal dysmotility. RESULTS Skeletal muscle biopsy revealed ragged-red and cytochrome- c oxidase-deficient fibers, and Southern blot analysis showed multiple mtDNA deletions. No deletions were detected in fibroblasts, and the results of quantitative polymerase chain reaction showed that the amount of mtDNA was normal in both muscle and fibroblasts. Exome sequencing using a mitochondrial library revealed compound heterozygous MPV17 mutations (p.LysMet88-89MetLeu and p.Leu143*), a novel cause of mtDNA multiple deletions. CONCLUSIONS In addition to causing juvenile-onset disorders with mtDNA depletion, MPV17 mutations can cause adult-onset multisystemic disease with multiple mtDNA deletions.

MPV17突变导致多线粒体DNA缺失的成人发病多系统疾病。
目的探讨成人发病的多系统线粒体DNA (mtDNA)缺失的病因。设计案例报告。设置大学医院。65岁男性,轴索感觉运动周围神经病变,上睑下垂,眼瘫,糖尿病,运动不耐受,脂肪性肝病,抑郁症,帕金森病,胃肠运动障碍。结果骨骼肌活检显示纤维呈不规则红色和细胞色素c氧化酶缺陷,Southern blot分析显示多个mtDNA缺失。在成纤维细胞中未检测到缺失,定量聚合酶链反应结果显示,肌细胞和成纤维细胞中mtDNA的量均正常。利用线粒体文库进行外显子组测序,发现复合杂合MPV17突变(p.LysMet88-89MetLeu和p.Leu143*),这是mtDNA多重缺失的新原因。结论:MPV17突变除了引起mtDNA缺失的青少年发病疾病外,还可引起成人发病的多系统疾病,伴有多个mtDNA缺失。
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来源期刊
Archives of neurology
Archives of neurology 医学-临床神经学
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