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Case Reports
. 2017 May 11:12:23-27.
doi: 10.1016/j.ymgmr.2017.05.001. eCollection 2017 Sep.

Novel recessive mutations in COQ4 cause severe infantile cardiomyopathy and encephalopathy associated with CoQ10 deficiency

Neal Sondheimer  1 , Stacy Hewson  1 , Jessie M Cameron  2 , Gino R Somers  2 , Jane Dunning Broadbent  3 , Marcello Ziosi  4 , Catarina Maria Quinzii  4 , Ali B Naini  3   4
Affiliations
Case Reports

Novel recessive mutations in COQ4 cause severe infantile cardiomyopathy and encephalopathy associated with CoQ10 deficiency

Neal Sondheimer et al. Mol Genet Metab Rep. .

Abstract

Coenzyme Q10 (CoQ10) or ubiquinone is one of the two electron carriers in the mitochondrial respiratory chain which has an essential role in the process of oxidative phosphorylation. Defects in CoQ10 synthesis are usually associated with the impaired function of CoQ10-dependent complexes I, II and III. The recessively transmitted CoQ10 deficiency has been associated with a number of phenotypically and genetically heterogeneous groups of disorders manifesting at variable age of onset. The infantile, multisystemic presentation is usually caused by mutations in genes directly involved in CoQ10 biosynthesis. To date, mutations in COQ1 (PDSS1 and PDSS2), COQ2, COQ4, COQ6, COQ7, COQ8A/ADCK3, COQ8B/ADCK4, and COQ9 genes have been identified in patients with primary form of CoQ10 deficiency. Here we report novel mutations in the COQ4 gene, which were identified in an infant with profound mitochondrial disease presenting with perinatal seizures, hypertrophic cardiomyopathy and severe muscle CoQ10 deficiency.

Keywords: CoQ10 deficiency; CoQ4; Encephalomyopathy; Infantile cardiomyopathy; Whole exome sequencing.

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Figures

Fig. 1.
Fig. 1
Electron micrographs of cardiac muscle show strikingly abnormal mitochondrial morphology, with unusual semi-circular arrangements of crista noted in multiple myofiber mitochondria, which are non-artefactual in nature. A & B, transmission electron microscopy, A × 17,200; B × 57,500.
Fig. 2.
Fig. 2
Family pedigree and location of CoQ4 mutations. A. Family pedigree showing inheritance of mutations identified in this study. B. Location of mutations on CoQ4 gene (novel mutations described here are shown in bold).
Fig. 3.
Fig. 3
A. Representative Western blot showing the level of CoQ4 protein in skin fibroblasts from patient (left) and control (right). B. Relative level of protein normalized to vinculin. C. Relative level of CoQ4 transcript normalized to GAPDH. Error bars represent standard deviations of six experiments. Mann-Whitney U test. **Indicates a value of p > 0.01.
See this image and copyright information in PMC

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