Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: OSMR

Green List (high evidence)

Samra et al. identified 10 affected individuals from seven unrelated families with germline biallelic loss-of-function variants in OSMR who shared a phenotype of early-onset, severe, widespread atopic dermatitis with peripheral eosinophilia and markedly elevated serum IgE. All patient-derived OSMRβ variants failed to localize to the cell surface, resulting in selective loss of OSM-dependent signaling. Patient cells showed markedly reduced OSM-induced phosphorylation of STAT1, STAT3, and STAT5, while signaling through other IL-6 family receptor complexes remained intact. Transcriptomic profiling of patient primary dermal fibroblasts revealed consistent downstream effects, including loss of interferon-responsive and inflammatory gene programs. Re-expression of wild-type OSMR restored receptor surface expression, STAT activation, and transcriptional responses, confirming a causal loss-of-function mechanism. Together, these findings establish biallelic OSMR deficiency as a novel primary atopic disorder.
Sources: Literature

Created: 17 Jun 2026, 2:02 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Atopic dermatitis; eosinophilia; elevated IgE

Publications

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