دورية أكاديمية
Human COQ4 deficiency: Delineating the clinical, metabolic and neuroimaging phenotypes.
| العنوان: | Human COQ4 deficiency: Delineating the clinical, metabolic and neuroimaging phenotypes. |
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| المؤلفون: | Laugwitz, L., Seibt, A., Herebian, D., Peralta, S., Kienzle, I., Buchert, R., Falb, R., Gauck, D., Müller, A., Grimmel, M., Beck-Woedel, S., Kern, J., Daliri, K., Katibeh, P., Danhauser, K., Leiz, S., Alesi, V., Baertling, F., Vasco, G., Steinfeld, R., Wagner, M., Caglayan, A.O., Gumus, H., Burmeister, M., Mayatepek, E., Martinelli, D., Tamhankar, P.M., Tamhankar, V., Joset, P., Steindl, K., Rauch, A., Bonnen, P.E., Froukh, T., Groeschel, S., Krägeloh-Mann, I., Haack, T.B., Distelmaier, F. |
| المصدر: | J. Med. Genet., DOI:10.1136/jmedgenet-2021-107729 (2021) |
| بيانات النشر: | Bmj Publishing Group |
| سنة النشر: | 2021 |
| المجموعة: | PuSH - Publikationsserver des Helmholtz Zentrums München |
| مصطلحات موضوعية: | Nervous System Diseases, Pediatrics, Epilepsy, Early Diagnosis |
| الوصف: | Background Human coenzyme Q4 (COQ4) is essential for coenzyme Q(10) (CoQ(10)) 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 CoQ(10) 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 CoQ(10) supplementation, alternative treatment strategies are warranted. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 0022-2593 1468-6244 |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/34656997; info:eu-repo/semantics/altIdentifier/wos/WOS:000725042300001; info:eu-repo/semantics/altIdentifier/isbn/0022-2593; info:eu-repo/semant; https://push-zb.helmholtz-muenchen.de/frontdoor.php?source_opus=63760Test; urn:isbn:0022-2593; urn:issn:0022-2593; urn:issn:1468-6244 |
| DOI: | 10.1136/jmedgenet-2021-107729 |
| الإتاحة: | https://doi.org/10.1136/jmedgenet-2021-107729Test https://push-zb.helmholtz-muenchen.de/frontdoor.php?source_opus=63760Test |
| حقوق: | info:eu-repo/semantics/closedAccess |
| رقم الانضمام: | edsbas.354DDD7E |
| قاعدة البيانات: | BASE |
| تدمد: | 00222593 14686244 |
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| DOI: | 10.1136/jmedgenet-2021-107729 |