2. Academic Validation
  3. The COQ2 genotype predicts the severity of coenzyme Q10 deficiency

The COQ2 genotype predicts the severity of coenzyme Q10 deficiency

  • Hum Mol Genet. 2016 Oct 1;25(19):4256-4265. doi: 10.1093/hmg/ddw257.
Maria Andrea Desbats 1 2,  Valeria Morbidoni 1 2,  Micol Silic-Benussi 3,  Mara Doimo 1 2,  Vincenzo Ciminale 3,  Matteo Cassina 1 2,  Sabrina Sacconi 4 5,  Michio Hirano 6,  Giuseppe Basso 7 2,  Fabien Pierrel 8 9,  Placido Navas 10,  Leonardo Salviati 1 2,  Eva Trevisson 11 2
Affiliations

Affiliations

  • 1 Clinical Genetics Unit, Department of Woman and Child Health, University of Padova, Padova, Italy.
  • 2 Istituto di Ricerca Pediatria, IRP, Città della Speranza, Padova, Italy.
  • 3 Istituto Oncologico Veneto IRCCS (IOV), Padova, Italy.
  • 4 Centre de référence des Maladies Neuromusculaires, Hôpital Archet 1, Nice, France.
  • 5 CNRS UMR7277, Inserm U1091, iBV - Institute of Biology Valrose, UNS Université Nice Sophia-Antipolis, Faculté de Médecine, Nice Cedex, France.
  • 6 Department of Neurology, Columbia University Medical Center, New York, NY, USA.
  • 7 Pediatric Hematology-Oncology Unit, Department of Woman and Child Health, University of Padova, Padova, Italy.
  • 8 University of Grenoble Alpes, Laboratoire Technologies de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications (TIMC-IMAG), Grenoble, France.
  • 9 Centre National de Recherche Scientifique (CNRS), TIMC-IMAG, Grenoble, France.
  • 10 Centro Andaluz de Biología del Desarrollo, CABD-CSIC, CIBERER, Instituto Carlos III, Universidad Pablo de Olavide, Sevilla, Spain.
  • 11 Clinical Genetics Unit, Department of Woman and Child Health, University of Padova, Padova, Italy eva.trevisson@unipd.it.
PMID: 27493029 DOI: 10.1093/hmg/ddw257
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.

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