Mutation of the mitochondrial carrier SLC25A42 causes a novel form of mitochondrial myopathy in humans

Myopathies are heterogeneous disorders characterized clinically by weakness and hypotonia, usually in the absence of gross dystrophic changes. Mitochondrial dysfunction is a frequent cause of myopathy. We report a simplex case born to consanguineous parents who presented with muscle weakness, lactic...

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Published inHuman genetics Vol. 135; no. 1; pp. 21 - 30
Main Authors Shamseldin, Hanan E., Smith, Laura L., Kentab, Amal, Alkhalidi, Hisham, Summers, Brady, Alsedairy, Haifa, Xiong, Yong, Gupta, Vandana A., Alkuraya, Fowzan S.
Format Journal Article
LanguageEnglish
Published Berlin/Heidelberg Springer Berlin Heidelberg 01.01.2016
Springer
Springer Nature B.V
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Summary:Myopathies are heterogeneous disorders characterized clinically by weakness and hypotonia, usually in the absence of gross dystrophic changes. Mitochondrial dysfunction is a frequent cause of myopathy. We report a simplex case born to consanguineous parents who presented with muscle weakness, lactic acidosis, and muscle changes suggestive of mitochondrial dysfunction. Combined autozygome and exome analysis revealed a missense variant in the SLC25A42 gene, which encodes an inner mitochondrial membrane protein that imports coenzyme A into the mitochondrial matrix. Zebrafish slc25a42 knockdown morphants display severe muscle disorganization and weakness. Importantly, these features are rescued by normal human SLC25A42 RNA, but not by RNA harboring the patient’s variant. Our data support a potentially causal link between SLC25A42 mutation and mitochondrial myopathy in humans.
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ISSN:0340-6717
1432-1203
DOI:10.1007/s00439-015-1608-8