| Autor: |
Chear CT; Primary Immunodeficiency Unit, Allergy and Immunology Research Centre, Institute for Medical Research, National Institutes of Health, Ministry of Health Malaysia, Setia Alam 40170, Malaysia., El Farran BAK; Institute of Biological Sciences, Faculty of Science, Universiti Malaya, Kuala Lumpur 50603, Malaysia., Sham M; Pediatric Department, Kuala Lumpur Hospital, Ministry of Health Malaysia, Kuala Lumpur 50586, Malaysia., Ramalingam K; Pediatric Department, Taiping Hospital, Ministry of Health Malaysia, Taiping 34000, Malaysia., Noh LM; Pediatric Department, Kuala Lumpur Hospital, Ministry of Health Malaysia, Kuala Lumpur 50586, Malaysia., Ismail IH; Department of Paediatrics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Malaysia., Chiow MY; Institute of Biological Sciences, Faculty of Science, Universiti Malaya, Kuala Lumpur 50603, Malaysia., Baharin MF; Primary Immunodeficiency Unit, Allergy and Immunology Research Centre, Institute for Medical Research, National Institutes of Health, Ministry of Health Malaysia, Setia Alam 40170, Malaysia., Ripen AM; Primary Immunodeficiency Unit, Allergy and Immunology Research Centre, Institute for Medical Research, National Institutes of Health, Ministry of Health Malaysia, Setia Alam 40170, Malaysia., Mohamad SB; Institute of Biological Sciences, Faculty of Science, Universiti Malaya, Kuala Lumpur 50603, Malaysia.; Centre of Research in Systems Biology, Structural Bioinformatics and Human Digital Imaging (CRYSTAL), Universiti Malaya, Kuala Lumpur 50603, Malaysia. |
| Abstrakt: |
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. |
