Primary immunodeficiency or monogenic inflammatory bowel disease
Gene: STX11Comment 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, 4:35 p.m. | Last Modified: 14 Oct 2020, 4:35 p.m.
Panel Version: 2.318
The following PubMed IDs were added to entity STX11: 16582076;18710388;15703195. These publications have been associated with OMIM phenotype MIM#603552, 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
Publications
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
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): STX11 .PanelApp HGNC gene symbol check: STX11 . IUIS Disease: Syntaxin 11 deficiency (FHL4) . IUIS Inheritance: AR .T cells: N/A, .B cells: Normal, .IUIS Other affected cells: N/A. IUIS Associated features: Fever, HSM, cHLH, cytopenias, . IUIS Major category: Diseases of Immune Dysregulation. IUIS Subcategory: Familial Hemophagocytic Lymphohistiocytosis (FHL syndromes)Created: 2 Jul 2018, 10:35 a.m.
added early-onset tagCreated: 30 Apr 2018, 10:36 a.m.
from GeneReview PMID:20301617: Approx ~20% of Turkish/Kurdish families of FHL are FHL4 PMID:15703195, PMID:16278825. Biallelic pathogenic variants identified in other ethnic groups, albeit at a low frequency 8 PMID:20486178.Created: 30 Apr 2018, 10:35 a.m.
Comment on list classification: Changed status from Amber to Green, there are more than 3 unrelated cases to support the phenotype Familial hemophagocytic lymphohistiocytosis-4 (FHL4) is caused by homozygous mutation in the syntaxin-11 gene (STX11; 605014) on chromosome 6q24. From OMIM Publications include: 3 unrelated Pakistani children with FHL4, each born of consanguineous parents, Muller et al. (2014) PMID: 24459464 identified a homozygous missense mutation in STX11. In a mutation analysis in a group of 63 unrelated patients with FHL of different geographic origins, Zur Stadt et al. (2006) PMID: 15703195 found 6 mutations in the STX11 gene, all in patients of Kurdish origin. Rudd et al. (2006) PMID:16582076 analyzed the STX11 gene in 34 patients with FHL from 28 unrelated families in whom PRF1 mutations had been excluded, they also suggested that STX11 mutations may be associated with secondary malignancies as three of the children experienced more than 1 year in remission without specific treatment, which the authors stated was very uncommon in this disease. Two of the children developed severe psychomotor retardation, one developed acute myelodysplastic syndrome, and one developed acute myelogenous leukemia. They noted that a total of 13 individuals from 8 Turkish families had been shown to carry STX11 mutationsCreated: 30 Apr 2018, 10:15 a.m.
Added publications to support role of STX11 variants in Hemophagocytic lymphohistiocytosis, familial, 4Created: 30 Apr 2018, 10:14 a.m.
from OMIM: Familial hemophagocytic lymphohistiocytosis is an autosomal recessive disease that presents as a severe hyperinflammatory syndrome with activated macrophages and T lymphocytes. Zur Stadt et al. (2005) PMID: 15703195 mapped one form of FHL (FHL4; 603552) to chromosome 6q24 by homozygosity mapping. They identified a 5-bp deletion (605014.0001), a large genomic deletion (605014.0002), and a nonsense mutation (Q268X; 605014.0003) in the STX11 gene, which maps to the 6q24 region.Created: 30 Apr 2018, 10:11 a.m.
Comment on phenotypes: added OMIM MIMid and synonymsCreated: 30 Apr 2018, 10:06 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, 2:02 p.m.
Original metadata downloaded from ESID Registry. ESID_Gene_original: STX11, PanelApp HGNC gene symbol check: STX11, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Diseases of immune dysregulation / Hemophagocytic Lymphohistiocytosis (HLH) / Familial hemophagocytic lymphohistiocytosis syndromes (FHLH)Created: 17 Apr 2018, 12:29 p.m.
Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: STX11, GRID_Gene_Symbol: STX11, GRID_Transcript_ENS_Community submitted: ENST00000367568, GRID_Transcript_RefSeq: NM_003764.3, GRID_Transcript_ENS_used_on_Production: ENST00000367568Created: 17 Apr 2018, 12:12 p.m.
Publications
Gene: stx11 has been classified as Green List (High Evidence).
Source Other was added to STX11. Publications for gene STX11 were updated from 15703195; 16278825; 16582076; 24459464; 20301617 to 16278825; 18710388; 16582076; 20301617; 24459464; 15703195 Rating Changed from Green List (high evidence) to Red List (low evidence)
Source NHS GMS was added to STX11.
Source North West GLH was added to STX11.
Source London North GLH was added to STX11.
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 STX11 were set to Hemophagocytic lymphohistiocytosis, familial 4, 603552, FHL4, Familial hemophagocytic lymphohistiocytosis syndromes (FHLH), HPLH4, HLH4, Fever, HSM, cHLH, cytopenias,, Diseases of Immune Dysregulation
IUIS Classification February 2018 was added to STX11. Panel: Primary immunodeficiency disorders
Victorian Clinical Genetics Services was added to STX11. Panel: Primary immunodeficiency disorders
Gene: stx11 has been classified as Green List (High Evidence).
Phenotypes for STX11 were set to Hemophagocytic lymphohistiocytosis, familial 4, 603552; FHL4; Familial hemophagocytic lymphohistiocytosis syndromes (FHLH); HPLH4; HLH4
Publications for STX11 were set to 15703195; 16278825; 16582076; 24459464; 20301617
This gene has been classified as Green List (High Evidence).
Publications for STX11 were set to 15703195; 16278825; 16582076; 24459464
Phenotypes for STX11 were set to Hemophagocytic lymphohistiocytosis, familial, 4, 603552; FHL4; Familial hemophagocytic lymphohistiocytosis syndromes (FHLH); HPLH4; HLH4
This gene has been classified as Amber List (Moderate Evidence).
STX11 Source: GOSH PID 20171198 was removed from gene: STX11
ESID Registry 20171117 was added to STX11. Panel: Primary immunodeficiency disorders Phenotypes for gene STX11 were set to Hemophagocytic lymphohistiocytosis, familial, 4, Familial hemophagocytic lymphohistiocytosis syndromes (FHLH)
Phenotypes for gene STX11 were set to Hemophagocytic lymphohistiocytosis, familial, 4
GRID V2.0 was added to STX11. Panel: Primary immunodeficiency disorders Phenotypes for gene STX11 were set to Hemophagocytic lymphohistiocytosis, familial, 4
GOSH PID v.8.0 was added to STX11. Panel: Primary immunodeficiency disorders
STX11 was added to Primary immunodeficiency disorders panel. Sources: GOSH PID 20171198
STX11 was created by Louise Daugherty