{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T15:20:49Z","timestamp":1780672849721,"version":"3.54.1"},"reference-count":47,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,10,19]],"date-time":"2022-10-19T00:00:00Z","timestamp":1666137600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Health Malaysia","award":["NMRR-16-892-31023"],"award-info":[{"award-number":["NMRR-16-892-31023"]}]},{"name":"Ministry of Health Malaysia","award":["NMRR-20-2387-56356"],"award-info":[{"award-number":["NMRR-20-2387-56356"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>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 &gt; T,NP_065390:p.Ser32Cys) and was predicted as damaging by in silico prediction tools. The NFKBIA gene encodes for I\u03baB\u03b1, a member of nuclear factor kappa B (NF-\u03baB) inhibitors, playing an important role in regulating NF-\u03baB activity. The mutation occurred at the six degrons (Asp31-Ser36) in I\u03baB\u03b1 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 I\u03baB\u03b1 required for NF-\u03baB activation. Conclusion: Our analysis hints that the post-translational modification in the NFKBIA Ser32Cys mutant would alter the signaling pathway of NF-\u03baB. Our findings support the usefulness of WES in diagnosing IEIs and suggest the role of post-translational modification of I\u03baB\u03b1.<\/jats:p>","DOI":"10.3390\/genes13101900","type":"journal-article","created":{"date-parts":[[2022,10,19]],"date-time":"2022-10-19T20:32:23Z","timestamp":1666211543000},"page":"1900","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["A Novel De Novo NFKBIA Missense Mutation Associated to Ectodermal Dysplasia with Dysgammaglobulinemia"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7584-385X","authenticated-orcid":false,"given":"Chai Teng","family":"Chear","sequence":"first","affiliation":[{"name":"Primary Immunodeficiency Unit, Allergy and Immunology Research Centre, Institute for Medical Research, National Institutes of Health, Ministry of Health Malaysia, Setia Alam 40170, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3678-8616","authenticated-orcid":false,"given":"Bader Abdul Kader","family":"El Farran","sequence":"additional","affiliation":[{"name":"Institute of Biological Sciences, Faculty of Science, Universiti Malaya, Kuala Lumpur 50603, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Sham","sequence":"additional","affiliation":[{"name":"Pediatric Department, Kuala Lumpur Hospital, Ministry of Health Malaysia, Kuala Lumpur 50586, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kavetha","family":"Ramalingam","sequence":"additional","affiliation":[{"name":"Pediatric Department, Taiping Hospital, Ministry of Health Malaysia, Taiping 34000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1036-9333","authenticated-orcid":false,"given":"Lokman Mohd","family":"Noh","sequence":"additional","affiliation":[{"name":"Pediatric Department, Kuala Lumpur Hospital, Ministry of Health Malaysia, Kuala Lumpur 50586, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4614-0140","authenticated-orcid":false,"given":"Intan Hakimah","family":"Ismail","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei Yee","family":"Chiow","sequence":"additional","affiliation":[{"name":"Institute of Biological Sciences, Faculty of Science, Universiti Malaya, Kuala Lumpur 50603, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohd Farid","family":"Baharin","sequence":"additional","affiliation":[{"name":"Primary Immunodeficiency Unit, Allergy and Immunology Research Centre, Institute for Medical Research, National Institutes of Health, Ministry of Health Malaysia, Setia Alam 40170, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5690-8008","authenticated-orcid":false,"given":"Adiratna Mat","family":"Ripen","sequence":"additional","affiliation":[{"name":"Primary Immunodeficiency Unit, Allergy and Immunology Research Centre, Institute for Medical Research, National Institutes of Health, Ministry of Health Malaysia, Setia Alam 40170, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saharuddin Bin","family":"Mohamad","sequence":"additional","affiliation":[{"name":"Institute of Biological Sciences, Faculty of Science, Universiti Malaya, Kuala Lumpur 50603, Malaysia"},{"name":"Centre of Research in Systems Biology, Structural Bioinformatics and Human Digital Imaging (CRYSTAL), Universiti Malaya, Kuala Lumpur 50603, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1007\/s10875-020-00758-x","article-title":"Human Inborn Errors of Immunity: 2019 Update of the IUIS Phenotypical Classification","volume":"40","author":"Bousfiha","year":"2020","journal-title":"J. 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