title: The COQ2 genotype predicts the severity of coenzyme Q10 deficiency.
abstract: COQ2 (p-hydroxybenzoate polyprenyl transferase) encodes the enzyme required for the second step of the final reaction sequence of Coenzyme Q10(CoQ) biosynthesis. Its mutations represent a frequent cause of primary CoQ deficiency and have been associated with the widest clinical spectrum, ranging from fatal neonatal multisystemic disease to late-onset encephalopathy. However, the reasons of this variability are still unknown.We have characterized the structure of human COQ2, defined its subcellular localization and developed a yeast model to validate all the mutant alleles reported so far.Our findings show that the main functional transcript of COQ2 is shorter than what was previously reported and that its protein product localizes to mitochondria with the C-terminus facing the intermembrane space. Complementation experiments in yeast showed that the residual activity of the mutant proteins correlates with the clinical phenotypes observed in patients.We defined the structure of COQ2 with relevant implications for mutation screening in patients and demonstrated that, contrary to other COQ gene defects such as ADCK3, there is a correlation between COQ2 genotype and patient's phenotype.
authors: Clinical Genetics Unit, Department of Woman and Child Health, University of Padova, Padova, Italy.|Istituto di Ricerca Pediatria, IRP, Città della Speranza, Padova, Italy.
authors: Maria Andrea
authors: MA
authors: Desbats
authors: Clinical Genetics Unit, Department of Woman and Child Health, University of Padova, Padova, Italy.|Istituto di Ricerca Pediatria, IRP, Città della Speranza, Padova, Italy.
authors: Valeria
authors: V
authors: Morbidoni
authors: Istituto Oncologico Veneto IRCCS (IOV), Padova, Italy.
authors: Micol
authors: M
authors: Silic-Benussi
authors: Clinical Genetics Unit, Department of Woman and Child Health, University of Padova, Padova, Italy.|Istituto di Ricerca Pediatria, IRP, Città della Speranza, Padova, Italy.
authors: Mara
authors: M
authors: Doimo
authors: Istituto Oncologico Veneto IRCCS (IOV), Padova, Italy.
authors: Vincenzo
authors: V
authors: Ciminale
authors: Clinical Genetics Unit, Department of Woman and Child Health, University of Padova, Padova, Italy.|Istituto di Ricerca Pediatria, IRP, Città della Speranza, Padova, Italy.
authors: Matteo
authors: M
authors: Cassina
authors: Centre de référence des Maladies Neuromusculaires, Hôpital Archet 1, Nice, France.|CNRS UMR7277, Inserm U1091, iBV - Institute of Biology Valrose, UNS Université Nice Sophia-Antipolis, Faculté de Médecine, Nice Cedex, France.
authors: Sabrina
authors: S
authors: Sacconi
authors: Department of Neurology, Columbia University Medical Center, New York, NY, USA.
authors: Michio
authors: M
authors: Hirano
authors: Pediatric Hematology-Oncology Unit, Department of Woman and Child Health, University of Padova, Padova, Italy.|Istituto di Ricerca Pediatria, IRP, Città della Speranza, Padova, Italy.
authors: Giuseppe
authors: G
authors: Basso
authors: University of Grenoble Alpes, Laboratoire Technologies de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications (TIMC-IMAG), Grenoble, France.|Centre National de Recherche Scientifique (CNRS), TIMC-IMAG, Grenoble, France.
authors: Fabien
authors: F
authors: Pierrel
authors: Centro Andaluz de Biología del Desarrollo, CABD-CSIC, CIBERER, Instituto Carlos III, Universidad Pablo de Olavide, Sevilla, Spain.
authors: Placido
authors: P
authors: Navas
authors: Clinical Genetics Unit, Department of Woman and Child Health, University of Padova, Padova, Italy.|Istituto di Ricerca Pediatria, IRP, Città della Speranza, Padova, Italy.
authors: Leonardo
authors: L
authors: Salviati
authors: Clinical Genetics Unit, Department of Woman and Child Health, University of Padova, Padova, Italy eva.trevisson@unipd.it.|Istituto di Ricerca Pediatria, IRP, Città della Speranza, Padova, Italy.
authors: Eva
authors: E
authors: Trevisson
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000096:biosynthesis / Q000235:genetics*; D001259:Ataxia / Q000235:genetics* / Q000473:pathology; D005786:Gene Expression Regulation; D005838:Genotype; D006801:Humans; D008928:Mitochondria / Q000235:genetics / Q000473:pathology; D028361:Mitochondrial Diseases / Q000235:genetics* / Q000473:pathology; D018908:Muscle Weakness / Q000235:genetics* / Q000473:pathology; D050505:Mutant Proteins / Q000096:biosynthesis / Q000235:genetics*; D009154:Mutation; D012441:Saccharomyces cerevisiae / Q000235:genetics; D012720:Severity of Illness Index; D014451:Ubiquinone / Q000172:deficiency* / Q000235:genetics
chemical_list: D050505:Mutant Proteins; D014451:Ubiquinone; D019883:Alkyl and Aryl Transferases; C021386:4-hydroxybenzoate polyprenyltransferase