Pulmonary arterial hypertension

Gene: TBX4

Green List (high evidence)

TBX4 (T-box 4)
EnsemblGeneIds (GRCh38): ENSG00000121075
EnsemblGeneIds (GRCh37): ENSG00000121075
OMIM: 601719, Gene2Phenotype
TBX4 is in 7 panels

2 reviews

Arianna Tucci (Genomics England Curator)

Green List (high evidence)

Rated as green as 23592887 finds mutations in TBX4 in 6/30 children with small patella syndrome and PAH. Not a comopn cause of PAH in adults
Created: 21 Jun 2017, 3:33 p.m.

Publications

  • TBX4

Louise Daugherty (Genomics England Curator)

Green List (high evidence)

From GMS Respiratory Specialist Test Group webex call 18th Jan 2019 it was agreed there is enough evidence to rate this gene Green
Created: 21 Jan 2019, 10:06 p.m.
Initial gene list and info collated by Ian Berry Leeds Genetics Laboratory November 2018 on behalf of the GMS Respiratory specialist test group. Gene Symbol submitted: TBX4; Suggested initial gene rating: Green; Evidence for inclusion: Small patella syndrome & PAH in children (PMID: 23592887 ); Evidence for exclusion: none given; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none given
Created: 6 Dec 2018, 2:01 p.m.
Comment on list classification: Changed status from Amber to Green from expert review noted that PMID: 23592887 finds mutations in TBX4 in 6/30 children with small patella syndrome and PAH. Not a common cause of PAH in adults
Created: 22 Jun 2017, 8:18 a.m.
It was noted in PMID: 27694411 that TBX4 mutations seem to account for a very small proportion of PAH in adults and yet TBX4 mutations in childhood do not appear to cause more severe disease, making it unlikely that early death is the cause of the lower frequency in adults and noted that the frequency of PAH in cohorts of patients with small patella syndrome is very low, suggesting low penetrance of the PAH phenotype.
Created: 21 Jun 2017, 12:29 p.m.
Associated to childhood-onset pulmonary arterial hypertension, in PMID: 27587546 (2016) there are 66 cases of paediatric PAH sequenced for known PAH genes, mutations in BMPR2 were found in 12.5% of cases, ACVRL1 in 10% and TBX4 in 7.5%. There have also been reports of autosomal dominant mutations in the gene TBX4 in patients with PAH, usually in families affected by the small patella syndrome PMID: 23592887 (2013). However, there is some reservation as together with mutations in other non-BMPR2 genes account for less than 5% of PAH cases, at least in mainly adult cohorts PMID: 27694411
Created: 21 Jun 2017, 12:23 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Ischiocoxopodopatellar syndrome, 147891; Small patella syndrome; SPS; Idiopathic pulmonary arterial hypertension; IPAH; Heritable pulmonary arterial hypertension; HPAH; Pulmonary arterial hypertension;

Publications

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • NHS GMS
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
  • Illumina TruGenome Clinical Sequencing Services
  • Literature
Phenotypes
  • Ischiocoxopodopatellar syndrome, 147891
  • Small patella syndrome
  • SPS
  • Idiopathic pulmonary arterial hypertension
  • IPAH
  • Heritable pulmonary arterial hypertension
  • HPAH
  • Pulmonary arterial hypertension
OMIM
601719
Clinvar variants
Variants in TBX4
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

6 Dec 2018, Gel status: 3

Added New Source, Status Update

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to TBX4. Rating Changed from Green List (high evidence) to Green List (high evidence)

22 Jun 2017, Gel status: 4

panel promoted to version 1

Louise Daugherty (Genomics England Curator)

Panel reviews were assessed, and panel was revised according to reviews and further in-house curation.

22 Jun 2017, Gel status: 4

Gene classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

22 Jun 2017, Gel status: 2

Set publications

Louise Daugherty (Genomics England Curator)

Publications for TBX4 were set to 23592887; 27587546; 27694411

21 Jun 2017, Gel status: 2

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for TBX4 were set to Ischiocoxopodopatellar syndrome, 147891; Small patella syndrome; SPS; Idiopathic pulmonary arterial hypertension; IPAH; Heritable pulmonary arterial hypertension; HPAH; Pulmonary arterial hypertension

21 Jun 2017, Gel status: 2

Upload gene information

Louise Daugherty (Genomics England Curator)

TBX4 was added to Pulmonary arterial hypertensionpanel. Sources: Illumina TruGenome Clinical Sequencing Services,Radboud University Medical Center, Nijmegen

21 Jun 2017, Gel status: 2

Upload gene information

Louise Daugherty (Genomics England Curator)

TBX4 was added to Pulmonary arterial hypertensionpanel. Sources: Illumina TruGenome Clinical Sequencing Services,Radboud University Medical Center, Nijmegen

14 Jun 2017, Gel status: 0

Created

Louise Daugherty (Genomics England Curator)

TBX4 was created by LouiseD

14 Jun 2017, Gel status: 0

Added New Source

Louise Daugherty (Genomics England Curator)

TBX4 was added to Pulmonary arterial hypertensionpanel. Sources: Literature