A Novel De Novo NFKBIA Missense Mutation Associated to Ectodermal Dysplasia with Dysgammaglobulinemia.
Genes (Basel)
; 13(10)2022 10 19.
Article
em En
| MEDLINE
| ID: mdl-36292785
ABSTRACT
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_020529c.94A > T,NP_065390p.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.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Displasia Ectodérmica
/
Disgamaglobulinemia
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Síndrome de Imunodeficiência com Hiper-IgM
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Síndromes de Imunodeficiência
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article