ERBIN (ERBB2-interacting protein), encoded by ERBB2IP, is a scaffolding protein involved in TGF-β signaling, epithelial cell polarity, and immune regulation. Disruption of ERBIN function has been implicated in atopic disorders and may overlap with hyper-IgE syndromes (HIES) due to impaired regulation of Th17 and Th2 pathways.
We report a patient with a clinical phenotype characterized by markedly elevated serum IgE levels (>5,000 IU/mL), recurrent pneumonias, recurrent bronchitis, atopic dermatitis since infancy, and allergic rhinitis. He also presented with a peculiar facial appearance but no skeletal abnormalities. The HIES score was 30, supporting a HIES-like phenotype. Family history is positive for moderate allergic rhinitis. Genetic testing through targeted next-generation sequencing revealed a heterozygous missense variant in ERBIN: c.4178T>C (p.Ile1393Thr), located in the leucine-rich repeat (LRR) domain, which is critical for protein–protein interactions. According to the American College of Medical Genetics and Genomics criteria, this variant is classified as a “variant of uncertain significance” supported by PM1 and PM2. Further functional studies are required to determine the pathogenicity of this variant.
The identified ERBIN variant may alter its scaffolding function, leading to dysregulated TGF-β signaling, impaired Treg function, and enhanced Th2 responses. This immune imbalance likely contributes to severe atopy, impaired defense against respiratory pathogens, and susceptibility to infections. The reduction in Th17 cells may further compromise mucosal immunity, a feature overlapping with STAT3-HIES but without the full syndromic spectrum.
This case adds to the emerging role of ERBIN mutations in Hyper-IgE-like disorders, underscoring the need to consider ERBIN variants in patients with severe atopic dermatitis, elevated IgE, and recurrent infections. Genetic testing may facilitate accurate diagnosis and guide personalized treatment approaches.
