Clefting
Gene: TBX1
The rating of this gene has been updated to Green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown following NHS Genomic Medicine Service approval.Created: 11 Oct 2023, 9:26 a.m. | Last Modified: 11 Oct 2023, 9:26 a.m.
Panel Version: 4.100
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Comment on list classification: Following consultation with Helen Brittain (Genomics England Clinical Team) it was agreed that there is sufficient evidence to promote this gene to Green on this panel (at least three cases of palatal involvement) at the next GMS panel update.Created: 14 Mar 2023, 11:41 a.m. | Last Modified: 14 Mar 2023, 11:41 a.m.
Panel Version: 3.9
TBX1 is encompassed by a region deleted in DiGeorge syndrome (22q11.2). There is some, albeit more limited, evidence linking SNVs with overlapping phenotypes.
Yagi et al 2003 (PMID: 14585638) found three cases with conotruncal anomaly face syndrome or DiGeorge's syndrome including velopharyngeal insufficiency of the cleft palate and/or thymus and parathyroid abnormalities but no cognitive deficits. Zweier et al., 2007 (PMID: 17273972) reported a heterozygous missense variant in a familial case of Shprintzen syndrome and Li et al., 2018 (PMID: 30137364) described two families with splice-altering variants in whom phenotypes ranged from isolated hypoparathyroidism (with reduced penetrance) to hypoparathyroidism with additional DiGeorge sequence-like features.
Also details about an addition case at NWGLH provided by Ronnie Wright on R15 panel. Patient harbouring a de novo final exon frameshift variant referred via immunology clinician and has clinical diagnosis of DiGeorge syndrome (prior 22q11 deletion testing negative).Created: 14 Mar 2023, 11:36 a.m. | Last Modified: 14 Mar 2023, 11:36 a.m.
Panel Version: 3.6
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
DiGeorge syndrome, OMIM:188400; Conotruncal anomaly face syndrome, OMIM:217095; Velocardiofacial syndrome, OMIM:192430
Publications
Radboud lists mutations in this gene as being linked to the clefting phenotype, as do several literature papers on DiGeorge syndrome, which encompassses cardiac and orofacial clefting phenotypes. However, these mutations are exclusively deletions of 22q11.2, and as the pipeline cannot currently cater for larger SVs, this gene is amber.Created: 31 May 2017, 3:30 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
CONOTRUNCAL HEART MALFORMATIONS; CTHM
Tag Q1_23_promote_green was removed from gene: TBX1.
Source Expert Review Green was added to TBX1. Source NHS GMS was added to TBX1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Gene: tbx1 has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: TBX1 were changed from CONOTRUNCAL HEART MALFORMATIONS; CTHM; Cleft palate to DiGeorge syndrome, OMIM:188400; Conotruncal anomaly face syndrome, OMIM:217095; Velocardiofacial syndrome, OMIM:192430
Publications for gene: TBX1 were set to
Tag Q1_23_promote_green tag was added to gene: TBX1.
Victorian Clinical Genetics Services was added to TBX1. Panel: Clefting Phenotypes for gene TBX1 were set to CONOTRUNCAL HEART MALFORMATIONS, CTHM, Cleft palate
Panel reviews were assessed, and panel was revised according to reviews and further curation 31st May 2017
TBX1 was added to Cleftingpanel. Sources: Expert Review Amber
TBX1 was created by ellenmcdonagh