1. Rescue of primary ubiquinone deficiency due to a novel COQ7 defect using 2,4-dihydroxybensoic acid.
- Author
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Freyer C, Stranneheim H, Naess K, Mourier A, Felser A, Maffezzini C, Lesko N, Bruhn H, Engvall M, Wibom R, Barbaro M, Hinze Y, Magnusson M, Andeer R, Zetterström RH, von Döbeln U, Wredenberg A, and Wedell A
- Subjects
- Amino Acid Sequence, Ataxia diagnosis, Ataxia drug therapy, Child, Child, Preschool, Chromatography, Liquid, DNA Mutational Analysis, Exome, Homozygote, Humans, Infant, Newborn, Male, Mitochondria genetics, Mitochondria metabolism, Mitochondrial Diseases diagnosis, Mitochondrial Diseases drug therapy, Molecular Sequence Data, Muscle Weakness diagnosis, Muscle Weakness drug therapy, Sequence Alignment, Tandem Mass Spectrometry, Ubiquinone genetics, Ataxia genetics, Hydroxybenzoates therapeutic use, Mitochondrial Diseases genetics, Muscle Weakness genetics, Mutation, Missense, Ubiquinone deficiency
- 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., Conclusion: We report the first patient with primary coenzyme Q deficiency due to a homozygous COQ7 mutation and a potentially beneficial treatment using 2,4DHB., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)
- Published
- 2015
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