Rescue of Primary Ubiquinone Deficiency Due to a Novel COQ7 Defect Using 2,4-dihydroxybensoic Acid

Overview

Journal J Med Genet

Specialty Genetics

Date 2015 Jun 19

PMID 26084283

Citations 57

Authors

Christoph Freyer

Henrik Stranneheim

Karin Naess

Arnaud Mourier

Andrea Felser

Camilla Maffezzini

Nicole Lesko

Helene Bruhn

Martin Engvall

Rolf Wibom

Michela Barbaro

Yvonne Hinze

Mans Magnusson

Robin Andeer

Rolf H Zetterstrom

Ulrika von Dobeln

Anna Wredenberg

Anna Wedell

Affiliations

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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.

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