BACKGROUND: COQ4 encodes a protein that organises the multienzyme complex for the synthesis of coenzyme Q(10) (CoQ(10)). A 3.9 Mb deletion of chromosome 9q34.13 was identified in a 3-year-old boy with mental retardation, encephalomyopathy and dysmorphic features. Because the deletion encompassed COQ4, the patient was screened for CoQ(10) deficiency. METHODS: A complete molecular and biochemical characterisation of the patient's fibroblasts and of a yeast model were performed. RESULTS: The study found reduced COQ4 expression (48% of controls), CoQ(10) content and biosynthetic rate (44% and 43% of controls), and activities of respiratory chain complex II+III. Cells displayed a growth defect that was corrected by the addition of CoQ(10) to the culture medium. Knockdown of COQ4 in HeLa cells also resulted in a reduction of CoQ(10.) Diploid yeast haploinsufficient for COQ4 displayed similar CoQ deficiency. Haploinsufficency of other genes involved in CoQ(10) biosynthesis does not cause CoQ deficiency, underscoring the critical role of COQ4. Oral CoQ(10) supplementation resulted in a significant improvement of neuromuscular symptoms, which reappeared after supplementation was temporarily discontinued. CONCLUSION: Mutations of COQ4 should be searched for in patients with CoQ(10) deficiency and encephalomyopathy; patients with genomic rearrangements involving COQ4 should be screened for CoQ(10) deficiency, as they could benefit from supplementation.
BACKGROUND:COQ4 encodes a protein that organises the multienzyme complex for the synthesis of coenzyme Q(10) (CoQ(10)). A 3.9 Mb deletion of chromosome 9q34.13 was identified in a 3-year-old boy with mental retardation, encephalomyopathy and dysmorphic features. Because the deletion encompassed COQ4, the patient was screened for CoQ(10) deficiency. METHODS: A complete molecular and biochemical characterisation of the patient's fibroblasts and of a yeast model were performed. RESULTS: The study found reduced COQ4expression (48% of controls), CoQ(10) content and biosynthetic rate (44% and 43% of controls), and activities of respiratory chain complex II+III. Cells displayed a growth defect that was corrected by the addition of CoQ(10) to the culture medium. Knockdown of COQ4 in HeLa cells also resulted in a reduction of CoQ(10.) Diploid yeasthaploinsufficient for COQ4 displayed similar CoQ deficiency. Haploinsufficency of other genes involved in CoQ(10) biosynthesis does not cause CoQ deficiency, underscoring the critical role of COQ4. Oral CoQ(10) supplementation resulted in a significant improvement of neuromuscular symptoms, which reappeared after supplementation was temporarily discontinued. CONCLUSION: Mutations of COQ4 should be searched for in patients with CoQ(10) deficiency and encephalomyopathy; patients with genomic rearrangements involving COQ4 should be screened for CoQ(10) deficiency, as they could benefit from supplementation.
Authors: Adam M Deutschbauer; Daniel F Jaramillo; Michael Proctor; Jochen Kumm; Maureen E Hillenmeyer; Ronald W Davis; Corey Nislow; Guri Giaever Journal: Genetics Date: 2005-02-16 Impact factor: 4.562
Authors: Seema R Lalani; Georgirene D Vladutiu; Katie Plunkett; Timothy E Lotze; Adekunle M Adesina; Fernando Scaglia Journal: Arch Neurol Date: 2005-02
Authors: José M López-Martín; Leonardo Salviati; Eva Trevisson; Giovanni Montini; Salvatore DiMauro; Catarina Quinzii; Michio Hirano; Angeles Rodriguez-Hernandez; Mario D Cordero; José A Sánchez-Alcázar; Carlos Santos-Ocaña; Plácido Navas Journal: Hum Mol Genet Date: 2007-03-20 Impact factor: 6.150
Authors: Luis Carlos López; Markus Schuelke; Catarina M Quinzii; Tomotake Kanki; Richard J T Rodenburg; Ali Naini; Salvatore Dimauro; Michio Hirano Journal: Am J Hum Genet Date: 2006-10-27 Impact factor: 11.025
Authors: C Sobreira; M Hirano; S Shanske; R K Keller; R G Haller; E Davidson; F M Santorelli; A F Miranda; E Bonilla; D S Mojon; A A Barreira; M P King; S DiMauro Journal: Neurology Date: 1997-05 Impact factor: 9.910
Authors: Alberto Casarin; Jose Carlos Jimenez-Ortega; Eva Trevisson; Vanessa Pertegato; Mara Doimo; Maria Lara Ferrero-Gomez; Sara Abbadi; Rafael Artuch; Catarina Quinzii; Michio Hirano; Giuseppe Basso; Carlos Santos Ocaña; Placido Navas; Leonardo Salviati Journal: Biochem Biophys Res Commun Date: 2008-05-12 Impact factor: 3.575
Authors: S Di Giovanni; M Mirabella; A Spinazzola; P Crociani; G Silvestri; A Broccolini; P Tonali; S Di Mauro; S Servidei Journal: Neurology Date: 2001-08-14 Impact factor: 9.910
Authors: Min Peng; Marni J Falk; Volker H Haase; Rhonda King; Erzsebet Polyak; Mary Selak; Marc Yudkoff; Wayne W Hancock; Ray Meade; Ryoichi Saiki; Adam L Lunceford; Catherine F Clarke; David L Gasser Journal: PLoS Genet Date: 2008-04-25 Impact factor: 5.917
Authors: Letian X Xie; Mohammad Ozeir; Jeniffer Y Tang; Jia Y Chen; Sylvie-Kieffer Jaquinod; Marc Fontecave; Catherine F Clarke; Fabien Pierrel Journal: J Biol Chem Date: 2012-05-16 Impact factor: 5.157
Authors: Marco Spinazzi; Enrico Radaelli; Katrien Horré; Amaia M Arranz; Natalia V Gounko; Patrizia Agostinis; Teresa Mendes Maia; Francis Impens; Vanessa Alexandra Morais; Guillermo Lopez-Lluch; Lutgarde Serneels; Placido Navas; Bart De Strooper Journal: Proc Natl Acad Sci U S A Date: 2018-12-21 Impact factor: 11.205
Authors: Eugen Widmeier; Merlin Airik; Hannah Hugo; David Schapiro; Johannes Wedel; Chandra C Ghosh; Makiko Nakayama; Ronen Schneider; Agape M Awad; Anish Nag; Jang Cho; Markus Schueler; Catherine F Clarke; Rannar Airik; Friedhelm Hildebrandt Journal: J Am Soc Nephrol Date: 2019-02-08 Impact factor: 10.121