Clinical Report: Novel NFKBIA Variants in the N-terminal Region
Overview
This study identifies four patients with de novo heterozygous NFKBIA variants, revealing a consistent immunological profile despite variable clinical outcomes.
Background
Germline monoallelic gain-of-function variants in NFKBIA lead to a rare immunodeficiency syndrome, primarily characterized by ectodermal dysplasia and immune dysfunction. This study aims to clarify the phenotypic spectrum associated with newly identified NFKBIA variants.
Data Highlights
Variant
Clinical Outcome
Immunological Profile
p.G33D
Variable
Expanded naïve T/B cells
p.M37R
Variable
Expanded naïve T/B cells
p.M37K
Variable
Expanded naïve T/B cells
p.D31H
Variable
Expanded naïve T/B cells
Key Findings
Four patients exhibited de novo heterozygous NFKBIA variants.
Clinical severity varied from recurrent infections to severe multisystem disease.
All patients showed ectodermal abnormalities and a consistent lymphocyte phenotype.
Markedly delayed TNF-α-induced IκBα degradation was observed in patient PBMCs.
All mutant proteins suppressed TNF-α-induced NF-κB reporter activity more than wild-type IκBα.
Clinical Implications
Clinicians should consider the broad clinical spectrum when evaluating patients with suspected NFKBIA-related disorders.
Conclusion
This study identifies shared immunological features despite diverse clinical presentations.
