A new mitochondrial point mutation in the transfer RNA^Lys gene associated with progressive external ophthalmoplegia with impaired respiratory regulation

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• 作者：Joachim Wolf^a ; ^{wolfj@klilu.de} ; Bert Obermaier-Kusser^b ; Martina Jacobs^b ; Cornelia Milles^c ; Mario Mö ; rl^c ; Harald D. von Pein^d ; Armin J. Grau^a ; Matthias F. Bauer^b
• 关键词：Progressive external ophthalmoplegia ; Mitochondrial disorders ; Mitochondrial tRNA ; Mitochondrial DNA mutation ; Respiratory insufficiency
• 刊名：Journal of the Neurological Sciences
• 出版年：2012
• 期刊代码：178_0022510x
• 类别：med
• 出版时间：15 May, 2012
• 卷：316
• 期：1-2
• 页码：108-111
• 文件大小：275 K

摘要

We report a novel heteroplasmic point mutation G8299A in the gene for mitochondrial tRNA^Lys in a patient with progressive external ophthalmoplegia complicated by recurrent respiratory insufficiency. Biochemical analysis of respiratory chain complexes in muscle homogenate showed a combined complex I and IV deficiency. The transition does not represent a known neutral polymorphism and affects a position in the tRNA acceptor stem which is conserved in primates, leading to a destabilization of this functionally important domain. In vitro analysis of an essential maturation step of the tRNA transcript indicates the probable pathogenicity of this mutation. We hypothesize that there is a causal relationship between the novel G8299A transition and progressive external ophthalmoplegia with recurrent respiratory failure due to a depressed respiratory drive.