title: A mutation in para-hydroxybenzoate-polyprenyl transferase (COQ2) causes primary coenzyme Q10 deficiency.
abstract: Ubiquinone (coenzyme Q(10) or CoQ(10)) is a lipid-soluble component of virtually all cell membranes, where it functions as a mobile electron and proton carrier. CoQ(10) deficiency is inherited as an autosomal recessive trait and has been associated with three main clinical phenotypes: a predominantly myopathic form with central nervous system involvement, an infantile encephalomyopathy with renal dysfunction, and an ataxic form with cerebellar atrophy. In two siblings of consanguineous parents with the infantile form of CoQ(10) deficiency, we identified a homozygous missense mutation in the COQ2 gene, which encodes para-hydroxybenzoate-polyprenyl transferase. The A-->G transition at nucleotide 890 changes a highly conserved tyrosine to cysteine at amino acid 297 within a predicted transmembrane domain. Radioisotope assays confirmed a severe defect of CoQ(10) biosynthesis in the fibroblasts of one patient. This mutation in COQ2 is the first molecular cause of primary CoQ(10) deficiency.
authors.affiliation: Department of Neurology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
authors.forename: Catarina
authors.initials: C
authors.lastname: Quinzii
authors.forename: Ali
authors.initials: A
authors.lastname: Naini
authors.forename: Leonardo
authors.initials: L
authors.lastname: Salviati
authors.forename: Eva
authors.initials: E
authors.lastname: Trevisson
authors.forename: Placido
authors.initials: P
authors.lastname: Navas
authors.forename: Salvatore
authors.initials: S
authors.lastname: Dimauro
authors.forename: Michio
authors.initials: M
authors.lastname: Hirano
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000235:genetics*; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D002675:Child, Preschool; D003067:Coenzymes / Q000096:biosynthesis / Q000172:deficiency; D003545:Cysteine / Q000737:chemistry / Q000235:genetics; D005260:Female; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D007223:Infant; D008297:Male; D017237:Mitochondrial Encephalomyopathies / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D020125:Mutation, Missense; D014443:Tyrosine / Q000737:chemistry / Q000235:genetics; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000172:deficiency
chemical_list: D003067:Coenzymes; D014451:Ubiquinone; D014443:Tyrosine; D019883:Alkyl and Aryl Transferases; C021386:4-hydroxybenzoate polyprenyltransferase; C024989:coenzyme Q10; D003545:Cysteine