Human COQ4 deficiency: delineating the clinical, metabolic and neuroimaging phenotypes.
| Autor: | Laugwitz L; Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany.; Department of Neuropediatrics, Developmental Neurology and Social Pediatrics, University of Tübingen, Tübingen, Germany., Seibt A; Department of General Pediatrics, Neonatology and Pediatric Cardiology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany., Herebian D; Department of General Pediatrics, Neonatology and Pediatric Cardiology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany., Peralta S; Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany., Kienzle I; Department of Neuropediatrics, Developmental Neurology and Social Pediatrics, University of Tübingen, Tübingen, Germany., Buchert R; Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany., Falb R; Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany., Gauck D; Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany., Müller A; Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany., Grimmel M; Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany., Beck-Woedel S; Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany., Kern J; Department of Neuropediatrics, Developmental Neurology and Social Pediatrics, University of Tübingen, Tübingen, Germany., Daliri K; Child Developmental Center, Shiraz University of Medical Sciences, Shiraz, Iran.; Institute for Neurophysiology, University of Cologne, Medical Faculty, Cologne, Germany., Katibeh P; Child Developmental Center, Shiraz University of Medical Sciences, Shiraz, Iran., Danhauser K; Institute of Human Genetics, Technische Universität München, Munich, Germany.; Helmholtz Zentrum Muenchen, Deutsches Forschungszentrum fuer Gesundheit und Umwelt (GmbH), Neuherberg, Germany., Leiz S; Pediatric Neurology, Department of Pediatrics, Klinikum Dritter Orden, Munich, Germany., Alesi V; Laboratory of Medical Genetics, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy., Baertling F; Department of General Pediatrics, Neonatology and Pediatric Cardiology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany., Vasco G; Department of Neuroscience and Neurorehabilitation, Unit of Neurorehabilitation, IRCCS Bambino Gesù Children's Hospital, Rome, Italy., Steinfeld R; University Children's Hospital Zurich, Zurich, Switzerland., Wagner M; Institute of Human Genetics, Technische Universität München, Munich, Germany.; Helmholtz Zentrum Muenchen, Deutsches Forschungszentrum fuer Gesundheit und Umwelt (GmbH), Neuherberg, Germany., Caglayan AO; Department of Medical Genetics, School of Medicine, Dokuz Eylul University, Izmir, Turkey., Gumus H; Department of Pediatrics, Erciyes University School of Medicine, Kayseri, Turkey., Burmeister M; Michigan Neuroscience Institute, University of Michigan, Ann Arbor, Michigan, USA., Mayatepek E; Department of General Pediatrics, Neonatology and Pediatric Cardiology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany., Martinelli D; Division of Metabolism, Bambino Gesù Children's Hospital IRCCS, Rome, Italy., Tamhankar PM; Centre for Medical Genetics, Mulund, Mumbai, India., Tamhankar V; Centre for Medical Genetics, Mulund, Mumbai, India., Joset P; Medical Genetics, Institute of Medical Genetics and Pathology, University Hospital Basel, 4056 Basel, Switzerland., Steindl K; Institute of Medical Genetics, University of Zurich, Zurich, Switzerland., Rauch A; Institute of Medical Genetics, University of Zurich, Zurich, Switzerland., Bonnen PE; Human Genome Sequencing Center, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA., Froukh T; Department of Biotechnology and Genetic Engineering, Philadelphia University, Amman, Jordan., Groeschel S; Department of Neuropediatrics, Developmental Neurology and Social Pediatrics, University of Tübingen, Tübingen, Germany., Krägeloh-Mann I; Department of Neuropediatrics, Developmental Neurology and Social Pediatrics, University of Tübingen, Tübingen, Germany., Haack TB; Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany.; Center for Rare Disease, University of Tübingen, Tübingen, Germany., Distelmaier F; Department of General Pediatrics, Neonatology and Pediatric Cardiology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany Felix.Distelmaier@med.uni-duesseldorf.de. |
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| Jazyk: | angličtina |
| Zdroj: | Journal of medical genetics [J Med Genet] 2022 Sep; Vol. 59 (9), pp. 878-887. Date of Electronic Publication: 2021 Oct 16. |
| DOI: | 10.1136/jmedgenet-2021-107729 |
| Abstrakt: | Background: Human coenzyme Q4 (COQ4) is essential for coenzyme Q 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 CoQ 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 CoQ Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.) |
| Databáze: | MEDLINE |
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