title: Rescue of primary ubiquinone deficiency due to a novel COQ7 defect using 2,4-dihydroxybensoic acid.
abstract: BACKGROUND
  Coenzyme Q is an essential mitochondrial electron carrier, redox cofactor and a potent antioxidant in the majority of cellular membranes. Coenzyme Q deficiency has been associated with a range of metabolic diseases, as well as with some drug treatments and ageing.
  
  
  METHODS
  We used whole exome sequencing (WES) to investigate patients with inherited metabolic diseases and applied a novel ultra-pressure liquid chromatography-mass spectrometry approach to measure coenzyme Q in patient samples.
  
  
  RESULTS
  We identified a homozygous missense mutation in the COQ7 gene in a patient with complex mitochondrial deficiency, resulting in severely reduced coenzyme Q levels We demonstrate that the coenzyme Q analogue 2,4-dihydroxybensoic acid (2,4DHB) was able to specifically bypass the COQ7 deficiency, increase cellular coenzyme Q levels and rescue the biochemical defect in patient fibroblasts.
  
  
  CONCLUSIONS
  We report the first patient with primary coenzyme Q deficiency due to a homozygous COQ7 mutation and a potentially beneficial treatment using 2,4DHB.
authors.affiliation: Centre for Inherited Metabolic Diseases, Karolinska University Hospital, Stockholm, Sweden Max Planck Institute Biology of Ageing - Karolinska Institutet Laboratory, Division of Metabolic Diseases, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Christoph
authors.initials: C
authors.lastname: Freyer
authors.affiliation: Centre for Inherited Metabolic Diseases, Karolinska University Hospital, Stockholm, Sweden Department of Molecular Medicine and Surgery, Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Henrik
authors.initials: H
authors.lastname: Stranneheim
authors.affiliation: Centre for Inherited Metabolic Diseases, Karolinska University Hospital, Stockholm, Sweden Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Naess
authors.affiliation: Max Planck Institute for Biology of Ageing, Cologne, Germany.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Mourier
authors.affiliation: Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Andrea
authors.initials: A
authors.lastname: Felser
authors.affiliation: Max Planck Institute Biology of Ageing - Karolinska Institutet Laboratory, Division of Metabolic Diseases, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Camilla
authors.initials: C
authors.lastname: Maffezzini
authors.affiliation: Centre for Inherited Metabolic Diseases, Karolinska University Hospital, Stockholm, Sweden Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Nicole
authors.initials: N
authors.lastname: Lesko
authors.affiliation: Centre for Inherited Metabolic Diseases, Karolinska University Hospital, Stockholm, Sweden Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Helene
authors.initials: H
authors.lastname: Bruhn
authors.affiliation: Centre for Inherited Metabolic Diseases, Karolinska University Hospital, Stockholm, Sweden Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Martin
authors.initials: M
authors.lastname: Engvall
authors.affiliation: Centre for Inherited Metabolic Diseases, Karolinska University Hospital, Stockholm, Sweden Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Rolf
authors.initials: R
authors.lastname: Wibom
authors.affiliation: Centre for Inherited Metabolic Diseases, Karolinska University Hospital, Stockholm, Sweden Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Michela
authors.initials: M
authors.lastname: Barbaro
authors.affiliation: Max Planck Institute for Biology of Ageing, Cologne, Germany.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Hinze
authors.affiliation: Department of Molecular Medicine and Surgery, Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Måns
authors.initials: M
authors.lastname: Magnusson
authors.affiliation: Department of Molecular Medicine and Surgery, Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Robin
authors.initials: R
authors.lastname: Andeer
authors.affiliation: Centre for Inherited Metabolic Diseases, Karolinska University Hospital, Stockholm, Sweden Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Rolf H
authors.initials: RH
authors.lastname: Zetterström
authors.affiliation: Centre for Inherited Metabolic Diseases, Karolinska University Hospital, Stockholm, Sweden Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Ulrika
authors.initials: U
authors.lastname: von Döbeln
authors.affiliation: Centre for Inherited Metabolic Diseases, Karolinska University Hospital, Stockholm, Sweden Max Planck Institute Biology of Ageing - Karolinska Institutet Laboratory, Division of Metabolic Diseases, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Wredenberg
authors.affiliation: Centre for Inherited Metabolic Diseases, Karolinska University Hospital, Stockholm, Sweden Max Planck Institute Biology of Ageing - Karolinska Institutet Laboratory, Division of Metabolic Diseases, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden Department of Molecular Medicine and Surgery, Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Wedell
mesh_terms: D000595:Amino Acid Sequence; D001259:Ataxia / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002853:Chromatography, Liquid; D004252:DNA Mutational Analysis; D059472:Exome; D006720:Homozygote; D006801:Humans; D062385:Hydroxybenzoates / Q000627:therapeutic use*; D007231:Infant, Newborn; D008297:Male; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D028361:Mitochondrial Diseases / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D008969:Molecular Sequence Data; D018908:Muscle Weakness / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D020125:Mutation, Missense; D016415:Sequence Alignment; D053719:Tandem Mass Spectrometry; D014451:Ubiquinone / Q000172:deficiency* / Q000235:genetics
chemical_list: D062385:Hydroxybenzoates; D014451:Ubiquinone; C017704:beta-resorcylic acid; C030777:ubiquinone 7
keywords: Metabolic disorders; Molecular genetics