Primary immunodeficiency or monogenic inflammatory bowel disease
Gene: THBD
not sure if you want to include aHUS with the other complement defects under primary immune disorders - this is certainly in that groupCreated: 29 Jun 2018, 3:34 p.m.
Phenotypes
aHUS
Keep Amber until more info on gene and disease association, refer to external expert reviewCreated: 19 Jun 2018, 12:19 p.m.
Previous reviews of this gene from 2016 on the Atypical haemolytic uraemic syndrome panel state that "Associated with phenotype in OMIM, not in G2P. At least nine variants reported but multi-factorial influences prevent this gene from being made green at the moment" . A literature search did not result in further evidence of an association between THBD and and Atypical haemolytic uraemic syndrome. In addition, Osborne et al 2018 (29500241) performed analysis of 610 rare genetic variants from 6 centres in 13 genes including THBD from >3500 patients with atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathy. After comparing allele frequencies of variants in these genes with those found in the ExAC server, no association was found between the rare variants in THBD and aHUS.Created: 14 Jun 2018, 3:23 p.m.
Comment on list classification: Downgraded from Amber to Red. This gene is on the atypical haemolytic uraemic syndrome panel, in view of the rating there this gene should be rated as Red due to the evidences given on the atypical haemolytic uraemic syndrome panelCreated: 5 Jul 2018, 1:40 p.m.
OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): THBD .PanelApp HGNC gene symbol check: THBD . IUIS Disease: Thrombomodulin deficiency . IUIS Inheritance: AD .T cells: Absent TCR, all T cells, poor proliferation, .B cells: N/A, .IUIS Other affected cells: N/A. IUIS Associated features: Atypical hemolytic-uremic syndrome. IUIS Major category: Complement Deficiencies. IUIS Subcategory: N/ACreated: 2 Jul 2018, 10:35 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, 1:07 p.m.
Original metadata downloaded from ESID Registry. ESID_Gene_original: THBD, PanelApp HGNC gene symbol check: THBD, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Complement deficiencies / Complement deficiency / Thrombomodulin deficiencyCreated: 17 Apr 2018, 12:29 p.m.
Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: THBD, GRID_Gene_Symbol: THBD, GRID_Transcript_ENS_Community submitted: ENST00000377103, GRID_Transcript_RefSeq: NM_000361.2, GRID_Transcript_ENS_used_on_Production: ENST00000377103Created: 17 Apr 2018, 12:12 p.m.
Source IUIS Classification December 2019 was added to THBD. Mode of inheritance for gene THBD was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Added phenotypes Atypical hemolytic-uremic syndrome; Complement Deficiencies for gene: THBD Publications for gene THBD were updated from to 32048120; 32086639
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.
Gene: thbd has been classified as Red List (Low Evidence).
Gene: thbd has been classified as Red List (Low Evidence).
Phenotypes for gene THBD were set to Hemolytic uremic syndrome, atypical, susceptibility to, 6, Thrombomodulin deficiency, Atypical hemolytic-uremic syndrome, Complement Deficiencies
IUIS Classification February 2018 was added to THBD. Panel: Primary immunodeficiency disorders
Victorian Clinical Genetics Services was added to THBD. Panel: Primary immunodeficiency disorders
This gene has been classified as Amber List (Moderate Evidence).
ESID Registry 20171117 was added to THBD. Panel: Primary immunodeficiency disorders Phenotypes for gene THBD were set to Hemolytic uremic syndrome, atypical, susceptibility to, 6, Thrombomodulin deficiency
Phenotypes for gene THBD were set to Hemolytic uremic syndrome, atypical, susceptibility to, 6
THBD was added to Primary immunodeficiency disorders panel. Sources: GRID V2.0
THBD was created by Louise Daugherty