دورية أكاديمية
A Novel De Novo NFKBIA Missense Mutation Associated to Ectodermal Dysplasia with Dysgammaglobulinemia
| العنوان: | A Novel De Novo NFKBIA Missense Mutation Associated to Ectodermal Dysplasia with Dysgammaglobulinemia |
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| المؤلفون: | Chai Teng Chear, Bader Abdul Kader El Farran, Marina Sham, Kavetha Ramalingam, Lokman Mohd Noh, Intan Hakimah Ismail, Mei Yee Chiow, Mohd Farid Baharin, Adiratna Mat Ripen, Saharuddin Bin Mohamad |
| المصدر: | Genes, Vol 13, Iss 10, p 1900 (2022) |
| بيانات النشر: | MDPI AG, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Genetics |
| مصطلحات موضوعية: | hyper IgM-like phenotype, NFKBIA, IκBα, NF-κB, post-translational modification, Genetics, QH426-470 |
| الوصف: | Background: Inborn errors of immunity (IEIs) are comprised of heterogeneous groups of genetic disorders affecting immune function. In this report, a 17-month-old Malay patient suspected of having Hyper IgM syndrome, a type of IEIs, was described. However, the diagnosis of Hyper IgM syndrome was excluded by the normal functional studies and the mild features of ectodermal dysplasia observed from a further clinical phenotype inspection. Methods: Whole-exome sequencing (WES) was performed to unravel the causative mutation in this patient. Results: The variant analysis demonstrated a novel missense mutation in NFKBIA (NM_020529:c.94A > T,NP_065390:p.Ser32Cys) and was predicted as damaging by in silico prediction tools. The NFKBIA gene encodes for IκBα, a member of nuclear factor kappa B (NF-κB) inhibitors, playing an important role in regulating NF-κB activity. The mutation occurred at the six degrons (Asp31-Ser36) in IκBα which were evolutionarily conserved across several species. Prediction analysis suggested that the substitution of Ser32Cys may cause a loss of the phosphorylation site at residue 32 and a gain of the sumoylation site at residue 38, resulting in the alteration of post-translational modifications of IκBα required for NF-κB activation. Conclusion: Our analysis hints that the post-translational modification in the NFKBIA Ser32Cys mutant would alter the signaling pathway of NF-κB. Our findings support the usefulness of WES in diagnosing IEIs and suggest the role of post-translational modification of IκBα. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 13101900 2073-4425 |
| العلاقة: | https://www.mdpi.com/2073-4425/13/10/1900Test; https://doaj.org/toc/2073-4425Test |
| DOI: | 10.3390/genes13101900 |
| الوصول الحر: | https://doaj.org/article/1c931c06ad764ff6818aab1031ac972cTest |
| رقم الانضمام: | edsdoj.1c931c06ad764ff6818aab1031ac972c |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 13101900 20734425 |
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| DOI: | 10.3390/genes13101900 |