Rare genetic inflammatory skin disorders

Gene: OSMR

Green List (high evidence)

Comment on mode of inheritance: There are 8 unrelated individuals reported in literature with biallelic OSMR variants and syndromic atopic dermatitis with peripheral eosinophilia and markedly elevated serum IgE. Hence, the mode of inheritance should be updated from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted (associated with dominant Amyloidosis) to BOTH monoallelic and biallelic, autosomal or pseudoautosomal.

Created: 29 Jul 2026, 2:25 p.m. | Last Modified: 29 Jul 2026, 2:26 p.m.

Panel Version: 4.24

PMID: 41783139 Andersen et al., 2026
Study described a patient (57-year-old man of Caucasian Danish descent) presenting with elevated IgE levels, atopic eczema, chronic pulmonary aspergillosis, frequent secondary staphylococcal skin infections and pustules, and bone fractures. Blood profiling showed elevated IgE-expressing plasmablasts and peripheral T follicular helper cells and atypical memory B cells. WGS showed that P1 was homozygous for a missense OSMR variant c.1307T>A, p.Val436Asp.
A significant reduction in OSMR surface expression on patient dermal fibroblasts compared to controls was found by flow cytometry. A skin biopsy showed perivascular inflammation with lymphocytes and eosinophils but no amyloid deposits.

PMID: 42221229 Samra et al., 2026
Study identified 10 patients from 7 unrelated kindreds spanning Europe, South Asia, and the Arab world carrying complete biallelic loss-of-function OSMR variants, causing a distinct recessive primary atopic disorder rather than dominant amyloidosis. 4/7 families were consanguineous. Patients presented with early-onset, severe, widespread atopic dermatitis with peripheral eosinophilia and markedly elevated serum IgE.
OSMR variants detected were a mix of missense, stop-gain, and frameshift. Heterozygous parents were unaffected.
In 3 pedigrees (A, B, & C), the OSMR: c.1307T>A, p.Val436Asp variant was reported. It has MAF = 0.004260 in the European population, and 14 total homozygotes reported in gnomAD v4.1.1. However, available UKB clinical data for 9 of these p.Val436Asp homozygous individuals suggest enrichment of allergic disease or cutaneous features, including elevated peripheral eosinophil counts or percentages (3/9) and documented allergic or dermatologic diagnoses in several individuals. Other reported variants not present in gnomAD v4.

OSMR is associated with AD Amyloidosis, primary localized cutaneous, 1, OMIM:105250; no recessive association added in OMIM, G2P, or ClinGen (accessed 29th July 2026).

Created: 29 Jul 2026, 2:22 p.m. | Last Modified: 29 Jul 2026, 2:22 p.m.

Panel Version: 4.22

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
atopic eczema, MONDO:0004980

Publications

• 41783139
• 42221229

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
AMYLOIDOSIS, PRIMARY LOCALIZED CUTANEOUS, 1; PLCA1

Publications

• 18179886

Green List (high evidence)

This gene was part of an initial gene list collated by Thomas Cullup, GOSH and Veronica Kinsler, UCL, 25.Jan.2019 on behalf of the GMS Skin Specialist Test Group. Gene Symbol submitted: OSMR; Suggested initial gene rating: Green; Evidence for inclusion: none provided; Evidence for exclusion: none provided; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none provided.

Created: 31 Jan 2019, 2:02 p.m.

Variants in this GENE are reported as part of current diagnostic practice