Primary immunodeficiency or monogenic inflammatory bowel disease
Gene: STAT3
agree with green geneCreated: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
YES- this is covered on our targeted exomeCreated: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
Heterozygous hypomorphic variants cause hyper-IgE syndrome.
Heterozygous gain-of-function variants cause immune dysregulation and/or combined immunodeficiency, not always of early onsetCreated: 11 Jun 2018, 12:24 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mode of pathogenicity
Other
Comment on list classification: Changed rating of gene from Red to Green. This gene was rated as Green in v2.208 and incorrectly automatically demoted to Red in v2.209. This was due to a defect in the automatic PanelApp uploading tool when a set of publications was added to the panel with the source ‘Other’, and under certain conditions associated to previous sources listed, resulted in the rating of the gene being automatically changed when it should not have been.Created: 14 Oct 2020, 4:26 p.m. | Last Modified: 14 Oct 2020, 4:26 p.m.
Panel Version: 2.314
The following PubMed IDs were added to entity STAT3: 25349174;28402852;25359994;25038750. These publications have been associated with OMIM phenotype MIM#615952, which is listed for this entity, by the immunedysregulation subgroup of the Human Phenotype Ontology Immune Mediated Disorders Consortium (https://hpo-immune-mediated-disorders.groups.io/g/update) in August 2020.Created: 13 Oct 2020, 9:36 a.m. | Last Modified: 13 Oct 2020, 9:36 a.m.
Panel Version: 2.208
Mode of Inheritance: OMIM has only autosomal dominant, and I can find no evidence for autosomal recessive, but GRID has marked this gene as both AD and AR so leaving the MOI as this just now.Created: 3 May 2018, 9:56 p.m.
Added tag for early-onsetCreated: 1 May 2018, 10:19 p.m.
Comment on publications: Added publications supporting association with hyper-IgE syndrome and infantile-onset multisystem autoimmune disease-1.Created: 1 May 2018, 10:18 p.m.
Orphanet - Autosomal dominant hyper-IgE syndrome. In 70% of patients, the phenotype is associated with heterozygous mutations of the signal transducer and activator of transcription 3 gene (STAT3; 17q21.31).Created: 1 May 2018, 10:16 p.m.
Comment on list classification: OMIM describes > 3 cases of mutations in STAT3 in patients with hyper-IgE syndrome. Minegishi et al. (2007) (PMID: 17676033) found that 8 of 15 unrelated nonfamilial HIES patients had heterozygous STAT3 mutations. All 5 mutants were nonfunctional by themselves and showed dominant-negative effects when coexpressed with wildtype STAT3. Holland et al. (2007) (PMID: 17881745) identified missense mutations and single-codon in-frame deletions in STAT3 in 50 familial and sporadic cases of HIES. Flanagan et al. (2014) (PMID: 25038750) identified 4 different de novo heterozygous missense mutations in the STAT3 gene in 5 unrelated patients with infantile-onset multisystem autoimmune disease-1. Milner et al. (2015) (PMID: 25359994) identified 9 different heterozygous missense mutations in the STAT3 gene in 13 patients from 10 families with ADMIO1. Changing the rating of this gene from Amber to Green based on > 3 cases of likely disease causing mutations.Created: 1 May 2018, 10:09 p.m.
Comment on phenotypes: Added MIM IDs to the first two phenotypesCreated: 1 May 2018, 9:41 p.m.
Publications
Gene rating submitted by Kimberly Gilmour and Austen Worth on behalf of London North GLH for the GMS Immunology specialist test group. As discussed with the GMS Immunology Specialist Test Group during webex call 28th March 2019 and confirmed in follow up email 6th September the Specialist Test Group all agreed there is enough evidence to rate this gene Green.Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
Gene rating submitted by Tracy Briggs, David Gokhale and Abigal Rousseau on behalf of North West GLH for the GMS Immunology specialist test group. As discussed with the GMS Immunology Specialist Test Group during webex call 28th March 2019 and confirmed in follow up email on 20th June the Specialist Test Group all agreed there is enough evidence to rate this gene Green.Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): STAT3 .PanelApp HGNC gene symbol check: STAT3 . IUIS Disease: AD-HIES Job syndrome . IUIS Inheritance: AD LOF .T cells: Nl number, poor proliferation, .B cells: Normal, reduced switched and non-switched memory B cells, BAFF expression increased, .IUIS Other affected cells: N/A. IUIS Associated features: Distinctive facial features (broad nasal bridge), bacterial infections (boils and pulmonary abscesses, pneumatoceles) due to S. aureus, pulmonary aspergillus, Pneumocystis jirovecii, eczema, mucocutaneous candidiasis, hyperextensible joints, osteoporosis and bone fractures, scoliosis, retention of primary teeth, coronary and cerebral aneurysm formation. IUIS Major category: Combined immunodeficiencies with associated or syndromic features. IUIS Subcategory: Hyper IgE Syndromes (HIES). // OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): STAT3 .PanelApp HGNC gene symbol check: STAT3 . IUIS Disease: STAT3 GOF mutation . IUIS Inheritance: AD (GOF) .T cells: N/A, .B cells: Decreased, .IUIS Other affected cells: N/A. IUIS Associated features: Lymphoproliferation, solid organ autoimmunity, recurrent infections. IUIS Major category: Diseases of Immune Dysregulation. IUIS Subcategory: Regulatory T Cell DefectsCreated: 2 Jul 2018, 11:01 a.m.
Comment on phenotypes: from IUIS (unable to add to phenotype directly due to limited word count. Distinctive facial features broad nasal bridge, bacterial infections boils and pulmonary abscesses, pneumatoceles due to S aureus, pulmonary aspergillus, Pneumocystis jirovecii, eczema, mucocutaneous candidiasis, hyperextensible joints, osteoporosis and bone fractures, scoliosis, retention of primary teeth, coronary and cerebral aneurysm formation; Combined immunodeficiencies with associated or syndromic features;Lymphoproliferation, solid organ autoimmunity, recurrent infections; Diseases of Immune DysregulationCreated: 1 Jul 2018, 3:46 p.m.
Comment on mode of pathogenicity: from expert review comment: Heterozygous hypomorphic variants cause hyper-IgE syndrome. Heterozygous gain-of-function variants cause immune dysregulation and/or combined immunodeficiency, not always of early onsetCreated: 13 Jun 2018, 10:35 a.m.
Comment on mode of inheritance: changed MOI due to expert review commentCreated: 13 Jun 2018, 10:34 a.m.
This gene was absent from the original PanelApp PID panel dataset (review April 2018). However it was listed in external expert immunodeficiency diagnostic gene list(s)
GOSH or GRID. In this combined PID panel, this gene has been rated as AMBER and needs further curational review to assess pertinence prior to v1.Created: 19 Apr 2018, 2:11 p.m.
Original metadata downloaded from ESID Registry. ESID_Gene_original: STAT3 GOF, PanelApp HGNC gene symbol check: STAT3, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Diseases of immune dysregulation / Early-onset multi-organ autoimmune disease / Early-onset multi-organ autoimmune disease; Other well defined PIDs / Hyper IgE syndromes / Hyper IgE syndrome (HIES)Created: 17 Apr 2018, 12:29 p.m.
Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: STAT3, GRID_Gene_Symbol: STAT3, GRID_Transcript_ENS_Community submitted: ENST00000264657, GRID_Transcript_RefSeq: NM_139276.2, GRID_Transcript_ENS_used_on_Production: ENST00000264657Created: 17 Apr 2018, 12:12 p.m.
Gene: stat3 has been classified as Green List (High Evidence).
Source Other was added to STAT3. Publications for gene STAT3 were updated from 17676033; 17881745; 25038750; 25359994 to 28402852; 25349174; 17881745; 17676033; 25359994; 25038750 Rating Changed from Green List (high evidence) to Red List (low evidence)
Source NHS GMS was added to STAT3.
Source North West GLH was added to STAT3.
Source London North GLH was added to STAT3.
2018-07-12 Louise Daugherty (Genomics England Curator) promoted panel to v1.0. Reviews were assessed, and panel was revised according to expert reviews and further in-house curation based on PanelApp guidelines. Previous panels (A- or hypo-gammaglobulinaemia, Congenital neutropaenia, Agranulocytosis, Combined B and T cell defect, Inherited complement deficiency and SCID panels) that were merged with this panel, were checked again for any changes/new reviews prior to versioning of this panel, these merged panels are now retired/made internal.
Phenotypes for gene: STAT3 were set to Autoimmune disease, multisystem, infantile-onset, 1 615952; Hyper-IgE recurrent infection syndrome 147060; Autoimmune disease, multisystem, infantile-onset; Early-onset multi-organ autoimmune disease; Hyper IgE syndrome (HIES); Combined immunodeficiencies with associated or syndromic features; Diseases of Immune Dysregulation
IUIS Classification February 2018 was added to STAT3. Panel: Primary immunodeficiency disorders
Victorian Clinical Genetics Services was added to STAT3. Panel: Primary immunodeficiency disorders
Gene: stat3 has been classified as Green List (High Evidence).
Mode of inheritance for gene: STAT3 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mode of pathogenicity for gene: STAT3 was changed to Other - please provide details in the comments
Mode of inheritance for gene: STAT3 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for STAT3 were set to 17676033; 17881745; 25038750; 25359994
This gene has been classified as Green List (High Evidence).
Phenotypes for STAT3 were set to Autoimmune disease, multisystem, infantile-onset, 1 615952; Hyper-IgE recurrent infection syndrome 147060; Autoimmune disease, multisystem, infantile-onset; Early-onset multi-organ autoimmune disease; Hyper IgE syndrome (HIES)
Phenotypes for STAT3 were set to Autoimmune disease, multisystem, infantile-onset, 1; Hyper-IgE recurrent infection syndrome; Autoimmune disease, multisystem, infantile-onset; Early-onset multi-organ autoimmune disease; Hyper IgE syndrome (HIES)
This gene has been classified as Amber List (Moderate Evidence).
ESID Registry 20171117 was added to STAT3. Panel: Primary immunodeficiency disorders Phenotypes for gene STAT3 were set to Autoimmune disease, multisystem, infantile-onset, 1, Hyper-IgE recurrent infection syndrome, Autoimmune disease, multisystem, infantile-onset, Autoimmune disease, multisystem, infantile-onset, Early-onset multi-organ autoimmune disease, Hyper IgE syndrome (HIES)
Phenotypes for gene STAT3 were set to Autoimmune disease, multisystem, infantile-onset, 1, Hyper-IgE recurrent infection syndrome, Autoimmune disease, multisystem, infantile-onset, Autoimmune disease, multisystem, infantile-onset
GRID V2.0 was added to STAT3. Panel: Primary immunodeficiency disorders Model of inheritance for gene STAT3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Phenotypes for gene STAT3 were set to Autoimmune disease, multisystem, infantile-onset, 1, Hyper-IgE recurrent infection syndrome, Autoimmune disease, multisystem, infantile-onset
STAT3 Source: GOSH PID 20171195 was removed from gene: STAT3
GOSH PID v.8.0 was added to STAT3. Panel: Primary immunodeficiency disorders
STAT3 was added to Primary immunodeficiency disorders panel. Sources: GOSH PID 20171195
STAT3 was created by Louise Daugherty