COVID-19 researchGene: TBX1
Comment on list classification: After consultation with the Genomics England clinical team, keeping this gene as Amber. Further evidence is needed for the role of SNVs in TBX1 contributing to the PID phenotype.
Created: 19 Jun 2018, 9:35 a.m.
Comment on phenotypes: Added MIM identifier for DiGeorge Syndrome
Created: 14 Jun 2018, 2:16 p.m.
Comment on publications: Added publications relating to TBX1 variants and phenotypes
Created: 14 Jun 2018, 2:15 p.m.
In OMIM TBX1 is associated with DiGeorge Syndrome. Immunodeficiency is a clinical feature of this syndrome (Davies 2013 (PMID: 24198816)). Davies report that in 90% of cases of DiGeorge Syndrome have a typical 3 Mb deletion including over 30 different genes. There is some evidence that TBX1 is associated with the immunodeficiency phenotype. Yagi et al 2013 (PMID: 14585638) report on 13 patients from ten families who have the 22q11.2 syndrome phenotype (which includes DiGeorge Syndrome) but no detectable deletion of 22q11.2. Three new point mutations of TBX1 were discovered. These three mutations were not observed in 1110 normal, unrelated control chromosomes. Patient F2, with a point mutation resulting in a non-synonymous change G310S was diagnosed with DiGeorge's syndrome and his clinical phenotype included absent thymus suggesting a role for TBX1 in this phenotype. Jerome and Papaioannou, 2001 (PMID: 11242110) report that Tbx1-/- mice display a wide range of developmental anomalies including hypoplasia of the thymus. Overall there is not a strong degree of evidence from the literature that TBX1 variants alone are responsible for an immunodeficiency phenotype.
Created: 14 Jun 2018, 2:06 p.m.
OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): TBX1 .PanelApp HGNC gene symbol check: TBX1 . IUIS Disease: TBX1 deficiency . IUIS Inheritance: AD .T cells: N/A, .B cells: Normal, .IUIS Other affected cells: N/A. IUIS Associated features: Hypoparathyroidism, conotruncal cardiac malformation, velopalatal insufficiency, abnormal facies, intellectual disability. IUIS Major category: Combined immunodeficiencies with associated or syndromic features. IUIS Subcategory: Thymic Defects with Additional Congenital Anomalies
Created: 2 Jul 2018, 10:35 a.m.
This gene was present in the original PanelApp PID panel dataset (review in April 2018) rated as Red. The gene is present in the 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, 1:30 p.m.
Original metadata downloaded from ESID Registry. ESID_Gene_original: Del 22q11.2, PanelApp HGNC gene symbol check: TBX1, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Combined immunodeficiencies / Severe combined immunodeficiency (SCID) / Severe combined immunodeficiency (SCID); Other well defined PIDs / DiGeorge syndrome / DiGeorge syndrome
Created: 17 Apr 2018, 12:29 p.m.
Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: TBX1, GRID_Gene_Symbol: TBX1, GRID_Transcript_ENS_Community submitted: ENST00000332710, GRID_Transcript_RefSeq: NM_080647.1, GRID_Transcript_ENS_used_on_Production: ENST00000332710
Created: 17 Apr 2018, 12:12 p.m.
Comment on list classification: After reviewer ratings and comments, this should remain on the red list for now.
Created: 20 May 2016, 2:21 p.m.
I would chose amber, we have seen it in several patients and functional as well as immunological data suggests real (patient lacks thymus but not 22q by array, missense mutation identified), but haven't published so at the moment the data isn't there.
Created: 20 Oct 2015, 1:47 p.m.
TBX1 is among the genes in the region 22q11.21 deleted in di George syndrome, which sometimes causes SCID. The aetiologic role of TBX1 in this phenotype is not known. OMIM provides a specific ID for di George syndrome, 188400
Created: 19 Oct 2015, 8:03 p.m.
Source Expert Review Green was added to TBX1. Added phenotypes Hypoparathyroidism, conotruncal cardiac malformation, velopalatal insufficiency, abnormal facies, intellectual disability; DiGeorge syndrome 188400; Di George syndrome; T-B+ SCID; Severe combined immunodeficiency (SCID); Combined immunodeficiencies with associated or syndromic features for gene: TBX1 Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
gene: TBX1 was added gene: TBX1 was added to Viral susceptibility. Sources: ESID Registry 20171117,Victorian Clinical Genetics Services,GRID V2.0,IUIS Classification December 2019,SCID v1.6,IUIS Classification February 2018,Expert Review Amber Mode of inheritance for gene: TBX1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: TBX1 were set to 11242110; 24198816; 14585638; 32086639; 32048120 Phenotypes for gene: TBX1 were set to Hypoparathyroidism, conotruncal cardiac malformation, velopalatal insufficiency, abnormal facies, intellectual disability; DiGeorge syndrome 188400; Di George syndrome; T-B+ SCID; Severe combined immunodeficiency (SCID); Combined immunodeficiencies with associated or syndromic features