Lookup NU author(s): Professor Robert Taylor
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© 2017 Wiley Periodicals, Inc. Primary coenzyme Q10 (CoQ10; MIM# 607426) deficiencies are an emerging group of inherited mitochondrial disorders with heterogonous clinical phenotypes. Over a dozen genes are involved in the biosynthesis of CoQ10, and mutations in several of these are associated with human disease. However, mutations in COQ5 (MIM# 616359), catalyzing the only C-methylation in the CoQ10 synthetic pathway, have not been implicated in human disease. Here, we report three female siblings of Iraqi-Jewish descent, who had varying degrees of cerebellar ataxia, encephalopathy, generalized tonic-clonic seizures, and cognitive disability. Whole-exome and subsequent whole-genome sequencing identified biallelic duplications in the COQ5 gene, leading to reduced levels of CoQ10 in peripheral white blood cells of all affected individuals and reduced CoQ10 levels in the only muscle tissue available from one affected proband. CoQ10 supplementation led to clinical improvement and increased the concentrations of CoQ10 in blood. This is the first report of primary CoQ10 deficiency caused by loss of function of COQ5, with delineation of the clinical, laboratory, histological, and molecular features, and insights regarding targeted treatment with CoQ10 supplementation.
Author(s): Malicdan MCV, Vilboux T, Ben-Zeev B, Guo J, Eliyahu A, Pode-Shakked B, Dori A, Kakani S, Chandrasekharappa SC, Ferreira CR, Shelestovich N, Marek-Yagel D, Pri-Chen H, Blatt I, Niederhuber JE, He L, Toro C, Taylor RW, Deeken J, Yardeni T, Wallace DC, Gahl WA, Anikster Y
Publication type: Article
Publication status: Published
Journal: Human Mutation
Print publication date: 01/01/2018
Online publication date: 16/10/2017
Acceptance date: 11/09/2017
ISSN (print): 1059-7794
ISSN (electronic): 1098-1004
Publisher: John Wiley and Sons Inc.
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