Dataset Information

Human COQ4 deficiency: delineating the clinical, metabolic and neuroimaging phenotypes.

ABSTRACT:

Background

Human coenzyme Q4 (COQ4) is essential for coenzyme Q₁₀ (CoQ₁₀) biosynthesis. Pathogenic variants in COQ4 cause childhood-onset neurodegeneration. We aimed to delineate the clinical spectrum and the cellular consequences of COQ4 deficiency.

Methods

Clinical course and neuroradiological findings in a large cohort of paediatric patients with COQ4 deficiency were analysed. Functional studies in patient-derived cell lines were performed.

Results

We characterised 44 individuals from 36 families with COQ4 deficiency (16 newly described). A total of 23 different variants were identified, including four novel variants in COQ4. Correlation analyses of clinical and neuroimaging findings revealed three disease patterns: type 1: early-onset phenotype with neonatal brain anomalies and epileptic encephalopathy; type 2: intermediate phenotype with distinct stroke-like lesions; and type 3: moderate phenotype with non-specific brain pathology and a stable disease course. The functional relevance of COQ4 variants was supported by in vitro studies using patient-derived fibroblast lines. Experiments revealed significantly decreased COQ4 protein levels, reduced levels of cellular CoQ₁₀ and elevated levels of the metabolic intermediate 6-demethoxyubiquinone.

Conclusion

Our study describes the heterogeneous clinical presentation of COQ4 deficiency and identifies phenotypic subtypes. Cell-based studies support the pathogenic characteristics of COQ4 variants. Due to the insufficient clinical response to oral CoQ₁₀ supplementation, alternative treatment strategies are warranted.

SUBMITTER: Laugwitz L

PROVIDER: S-EPMC9807242 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Publications

Human COQ4 deficiency: delineating the clinical, metabolic and neuroimaging phenotypes.

Laugwitz Lucia L Seibt Annette A Herebian Diran D Peralta Susana S Kienzle Imke I Buchert Rebecca R Falb Ruth R Gauck Darja D Müller Amelie A Grimmel Mona M Beck-Woedel Stefanie S Kern Jan J Daliri Karim K Katibeh Pegah P Danhauser Katharina K Leiz Steffen S Alesi Viola V Baertling Fabian F Vasco Gessica G Steinfeld Robert R Wagner Matias M Caglayan Ahmet Okay AO Gumus Hakan H Burmeister Margit M Mayatepek Ertan E Martinelli Diego D Tamhankar Parag Mohan PM Tamhankar Vasundhara V Joset Pascal P Steindl Katharina K Rauch Anita A Bonnen Penelope E PE Froukh Tawfiq T Groeschel Samuel S Krägeloh-Mann Ingeborg I Haack Tobias B TB Distelmaier Felix F

Journal of medical genetics 20211016 9

<h4>Background</h4>Human coenzyme Q4 (COQ4) is essential for coenzyme Q<sub>10</sub> (CoQ<sub>10</sub>) biosynthesis. Pathogenic variants in <i>COQ4</i> cause childhood-onset neurodegeneration. We aimed to delineate the clinical spectrum and the cellular consequences of COQ4 deficiency.<h4>Methods</h4>Clinical course and neuroradiological findings in a large cohort of paediatric patients with COQ4 deficiency were analysed. Functional studies in patient-derived cell lines were performed.<h4>Resul ...[more]

PMID: 34656997

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Dataset Information

Human COQ4 deficiency: delineating the clinical, metabolic and neuroimaging phenotypes.

Background

Methods

Results

Conclusion

Publications

Human COQ4 deficiency: delineating the clinical, metabolic and neuroimaging phenotypes.

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