MPV17 mutation causes neuropathy and leukoencephalopathy with multiple mtDNA deletions in muscle

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• 作者：Emma L. Blakely^a ; Anna Butterworth^a ; Robert D.M. Hadden^b ; Istvan Bodi^c ; Langping He^a ; Robert McFarland^a ; Robert W. Taylor^a ; ^{robert.taylor@ncl.ac.uk}
• 关键词：Mitochondrial DNA ; mtDNA maintenance ; Multiple mtDNA deletions ; Neuropathy ; COX-deficient fibres
• 刊名：Neuromuscular Disorders
• 出版年：2012
• 期刊代码：203_09608966
• 类别：med
• 出版时间：July, 2012
• 卷：22
• 期：7
• 页码：587-591
• 文件大小：503 K

摘要

Disorders of mitochondrial DNA (mtDNA) maintenance are clinically and genetically heterogeneous, embracing recessive mtDNA depletion syndromes affecting children and adult-onset multiple mtDNA deletion disorders. Here we show that mutation of MPV17 - a gene implicated in severe, infantile hepatocerebral mtDNA depletion disorders characterised by a loss of mtDNA copies - can also cause clonally-expanded mtDNA deletion and focal cytochrome c oxidase (COX) deficiency in skeletal muscle associated with an adult presentation of neuropathy and leukoencephalopathy. The mpv17 protein is therefore intimately involved in both the mtDNA replication and repair processes and associated with both quantitative and qualitative mtDNA abnormalities.