Rescue of primary ubiquinone deficiency due to a novel COQ7 defect using 2,4–dihydroxybensoic acid
BackgroundCoenzyme 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.MethodsWe used whole exome...
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Published in | Journal of medical genetics Vol. 52; no. 11; pp. 779 - 783 |
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Main Authors | , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
England
BMJ Publishing Group LTD
01.11.2015
BMJ Publishing Group |
Series | Short report |
Subjects | |
Online Access | Get full text |
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Summary: | BackgroundCoenzyme 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.MethodsWe 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.ResultsWe 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.ConclusionWe report the first patient with primary coenzyme Q deficiency due to a homozygous COQ7 mutation and a potentially beneficial treatment using 2,4DHB. |
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Bibliography: | ObjectType-Case Study-2 SourceType-Scholarly Journals-1 ObjectType-Feature-4 content type line 23 ObjectType-Report-1 ObjectType-Article-3 ObjectType-Article-1 ObjectType-Feature-2 CF, HS and KN contributed equally to this work. |
ISSN: | 0022-2593 1468-6244 1468-6244 |
DOI: | 10.1136/jmedgenet-2015-102986 |