Activity
| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
14 actions
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary immunodeficiency or monogenic inflammatory bowel disease v9.33 | OSMR | Ida Ertmanska edited their review of gene: OSMR: Changed phenotypes to: atopic eczema, MONDO:0004980 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary immunodeficiency or monogenic inflammatory bowel disease v9.33 | OSMR | Ida Ertmanska Phenotypes for gene: OSMR were changed from Atopic dermatitis; eosinophilia; elevated IgE to Atopic dermatitis; eosinophilia; elevated IgE; atopic eczema, MONDO:0004980 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary immunodeficiency or monogenic inflammatory bowel disease v9.32 | OSMR | Ida Ertmanska Publications for gene: OSMR were set to 42221229 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary immunodeficiency or monogenic inflammatory bowel disease v9.31 | OSMR | Ida Ertmanska Classified gene: OSMR as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary immunodeficiency or monogenic inflammatory bowel disease v9.31 | OSMR | Ida Ertmanska Added comment: Comment on list classification: There are 8 unrelated patients reported in literature with biallelic OSMR variants and syndromic atopic dermatitis with peripheral eosinophilia and markedly elevated serum IgE. Hence, this gene can be promoted to Green at the next GMS update. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary immunodeficiency or monogenic inflammatory bowel disease v9.31 | OSMR | Ida Ertmanska Gene: osmr has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary immunodeficiency or monogenic inflammatory bowel disease v9.30 | OSMR | Ida Ertmanska Tag Q3_26_promote_green tag was added to gene: OSMR. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary immunodeficiency or monogenic inflammatory bowel disease v9.30 | OSMR |
Ida Ertmanska changed review comment from: 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 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.; to: 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 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). |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary immunodeficiency or monogenic inflammatory bowel disease v9.30 | OSM |
Ida Ertmanska gene: OSM was added gene: OSM was added to Primary immunodeficiency or monogenic inflammatory bowel disease. Sources: Literature Mode of inheritance for gene: OSM was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: OSM were set to 39847438 Phenotypes for gene: OSM were set to bone marrow disorder, MONDO:0003225 Review for gene: OSM was set to RED Added comment: PMID: 39847438 Garrigue et al., 2025 Report of 3 female sibs from a consanguineous family presenting with inherited severe bone marrow failure syndromes (IBMFS) characterized by profound anemia, thrombocytopenia, and neutropenia. Patients showed no susceptibility to infection, nor any bone or psychomotor defects. WES detected a homozygous OSM: c.507_508insG; Arg170AlafsTer124 variant in P1 and P2, confirmed het in unaffected parents. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary immunodeficiency or monogenic inflammatory bowel disease v9.29 | OSMR | Ida Ertmanska edited their review of gene: OSMR: Changed publications to: 41783139, 42221229 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary immunodeficiency or monogenic inflammatory bowel disease v9.29 | OSMR |
Ida Ertmanska changed review comment from: 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.; to: 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 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. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary immunodeficiency or monogenic inflammatory bowel disease v9.29 | OSMR |
Ida Ertmanska changed review comment from: 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.; to: 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. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary immunodeficiency or monogenic inflammatory bowel disease v9.29 | OSMR | Ida Ertmanska reviewed gene: OSMR: Rating: GREEN; Mode of pathogenicity: None; Publications: 42221229; Phenotypes: Amyloidosis, primary localized cutaneous, 1, OMIM:105250, atopic eczema, MONDO:0004980; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary immunodeficiency or monogenic inflammatory bowel disease v9.9 | OSMR |
Boaz Palterer gene: OSMR was added gene: OSMR was added to Primary immunodeficiency or monogenic inflammatory bowel disease. Sources: Literature Mode of inheritance for gene: OSMR was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: OSMR were set to 42221229 Phenotypes for gene: OSMR were set to Atopic dermatitis; eosinophilia; elevated IgE Penetrance for gene: OSMR were set to unknown Review for gene: OSMR was set to GREEN Added comment: 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 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||