title: Mutation of the mitochondrial carrier SLC25A42 causes a novel form of mitochondrial myopathy in humans.
abstract: 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.
authors.affiliation: Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: Hanan E
authors.initials: HE
authors.lastname: Shamseldin
authors.affiliation: Division of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Laura L
authors.initials: LL
authors.lastname: Smith
authors.affiliation: Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Amal
authors.initials: A
authors.lastname: Kentab
authors.affiliation: Department of Pathology, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Hisham
authors.initials: H
authors.lastname: Alkhalidi
authors.affiliation: Department of Molecular Biophysics & Biochemistry 260 Whitney Avenue P.O. Box 208114. New Haven, CT, USA.
authors.forename: Brady
authors.initials: B
authors.lastname: Summers
authors.affiliation: Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: Haifa
authors.initials: H
authors.lastname: Alsedairy
authors.affiliation: Department of Molecular Biophysics & Biochemistry 260 Whitney Avenue P.O. Box 208114. New Haven, CT, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Xiong
authors.affiliation: Division of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Vandana A
authors.initials: VA
authors.lastname: Gupta
authors.affiliation: Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.|Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.
authors.forename: Fowzan S
authors.initials: FS
authors.lastname: Alkuraya
mesh_terms: D033741:Adenine Nucleotide Translocator 1 / Q000235:genetics*; D000293:Adolescent; D000818:Animals; D005260:Female; D006801:Humans; D008297:Male; D017240:Mitochondrial Myopathies / Q000235:genetics*; D023421:Models, Animal; D009154:Mutation; D010375:Pedigree; D012333:RNA, Messenger / Q000235:genetics; D015027:Zebrafish
chemical_list: D033741:Adenine Nucleotide Translocator 1; D012333:RNA, Messenger; C580832:SLC25A4 protein, human