دورية أكاديمية
FOSL2 truncating variants in the last exon cause a neurodevelopmental disorder with scalp and enamel defects
| العنوان: | FOSL2 truncating variants in the last exon cause a neurodevelopmental disorder with scalp and enamel defects |
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| المؤلفون: | Cospain, A., Rivera-Barahona, A., Dumontet, E., Gener, B., Bailleul-Forestier, I., Meyts, I., Jouret, G., Isidor, B., Brewer, C., Wuyts, W., Moens, L., Delafontaine, S., Keung Lam, W. W., Van Den Bogaert, K., Boogaerts, A., Scalais, E., Besnard, T., Cogne, B., Guissard, C., Rollier, P., Carre, W., Bouvet, R., Tarte, K., Gómez-Carmona, R., Lapunzina, P., Odent, S., Faoucher, M., Dubourg, C., Ruiz-Pérez, V. L., Devriendt, K., Pasquier, L., Pérez-Jurado, L. A. |
| بيانات النشر: | Nature |
| سنة النشر: | 2023 |
| المجموعة: | RD&E Research Repository (Royal Devon and Exeter NHS Foundation Trust) |
| مصطلحات موضوعية: | Humans, Scalp/abnormalities/metabolism, Autism Spectrum Disorder/genetics, HEK293 Cells, Transcription Factor AP-1/genetics, Exons/genetics, Ectodermal Dysplasia/genetics, Neurodevelopmental Disorders/genetics, RNA, Messenger, Fos-Related Antigen-2/genetics, AP-1 complex, Adams-Oliver syndrome, Aplasia cutis congenita of scalp, Enamel hypoplasia, FOSL2, qGenomics Laboratories |
| الوصف: | PURPOSE: We aimed to investigate the molecular basis of a novel recognizable neurodevelopmental syndrome with scalp and enamel anomalies caused by truncating variants in the last exon of the gene FOSL2, encoding a subunit of the AP-1 complex. METHODS: Exome sequencing was used to identify genetic variants in all cases, recruited through Matchmaker exchange. Gene expression in blood was analyzed using reverse transcription polymerase chain reaction. In vitro coimmunoprecipitation and proteasome inhibition assays in transfected HEK293 cells were performed to explore protein and AP-1 complex stability. RESULTS: We identified 11 individuals from 10 families with mostly de novo truncating FOSL2 variants sharing a strikingly similar phenotype characterized by prenatal growth retardation, localized cutis scalp aplasia with or without skull defects, neurodevelopmental delay with autism spectrum disorder, enamel hypoplasia, and congenital cataracts. Mutant FOSL2 messenger RNAs escaped nonsense-mediated messenger RNA decay. Truncated FOSL2 interacts with c-JUN, thus mutated AP-1 complexes could be formed. CONCLUSION: Truncating variants in the last exon of FOSL2 associate a distinct clinical phenotype by altering the regulatory degradation of the AP-1 complex. These findings reveal a new role for FOSL2 in human pathology. ; RD&E staff can access the full-text of this article by clicking on the 'Additional Link' above and logging in with NHS OpenAthens if prompted. ; Accepted version (6 month embargo), submitted version |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://linkinghub.elsevier.com/retrieve/pii/S1098-3600Test(22)00937-6; Genet Med. 2022 Dec;24(12):2475-2486. doi:10.1016/j.gim.2022.09.002. Epub 2022 Oct 4.; https://rde.dspace-express.com/handle/11287/622737Test; Genetics in medicine |
| DOI: | 10.1016/j.gim.2022.09.002 |
| الإتاحة: | https://doi.org/10.1016/j.gim.2022.09.002Test https://rde.dspace-express.com/handle/11287/622737Test |
| حقوق: | Copyright © 2022 American College of Medical Genetics and Genomics. All rights reserved. |
| رقم الانضمام: | edsbas.197E042E |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.gim.2022.09.002 |
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