Thoracic aortic aneurysm or dissection (GMS)

Gene: FOXE3

Comment on mode of inheritance: All cases reported in PMID: 26854927 (Kuang et al 2016) are heterozygous so the MONOALLELIC mode of inheritance is appropriate for the Thoracic aortic aneurysms and acute aortic dissection phenotype.

Created: 1 Sep 2021, 2:32 p.m. | Last Modified: 1 Sep 2021, 2:32 p.m.

Panel Version: 1.16

I don't know

Rated as 'Uncertain' by ClinGen.

Created: 1 Jul 2020, 6:59 a.m. | Last Modified: 1 Jul 2020, 6:59 a.m.

Panel Version: 1.3

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Aortic aneurysm, familial thoracic 11, (susceptibility to) 617349

Publications

• 30071989

Green List (high evidence)

Submitted on behalf of the GMS Cardiology specialist group. This gene did not achieve a consensus Green rating; however, the group agreed that the existing evidence (published and in-house data) was sufficient to support inclusion in this panel.

Created: 9 Dec 2019, 1:19 p.m. | Last Modified: 9 Dec 2019, 1:19 p.m.

Panel Version: 0.55

I don't know

The rating of this gene has been updated following NHS Genomic Medicine Service approval.

Created: 3 Mar 2022, 1:06 p.m. | Last Modified: 3 Mar 2022, 1:06 p.m.

Panel Version: 1.23

Submitted on behalf of the GMS Cardiology specialist group. The group has agreed that this gene should be Amber on this panel.

Created: 18 Nov 2019, 4:33 p.m. | Last Modified: 18 Nov 2019, 4:33 p.m.

Panel Version: 0.35

I don't know

Associated with TAAD in Kuang 2016 J Clin Invest.

Created: 2 Oct 2019, 11:06 a.m. | Last Modified: 2 Oct 2019, 11:06 a.m.

Panel Version: 0.30

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

Phenotypes
Aortic aneurysm, familial thoracic 11, (susceptibility to) 617349

Publications

• 26854927

I don't know

On CGGL Royal Brompton TAAD currently, but no variants found so far. PMID:26854927 good evidence but probably need more for a green rating

Created: 18 Sep 2019, 7:42 p.m. | Last Modified: 18 Sep 2019, 7:42 p.m.

Panel Version: 0.30

Green List (high evidence)

617349 susceptibility to aortic aneurysm

Created: 25 Mar 2019, 4:30 p.m.

Kuang et al (J Clin Invest. 2016;126:948 PMID:26854927) describe several variants found in patients with TAAD. All variants associated with TAAD were located in the Forkhead domain. Segregation evidence for two of these variants but incomplete penetrance in that heterozygous male carriers are affected in this study but two heterozygous female carriers are unaffected. 8 family members affected with TAAD - all are male. Suggest FOXE3 mutations lead to reduced numbers of aortic smooth muscle cells and increased smooth muscle cell apoptosis in response to biomechanical stress.

Created: 25 Mar 2019, 4:27 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Variants in this GENE are reported as part of current diagnostic practice

I don't know

This gene was part of an initial gene list collated by Matthew Edwards Royal Brompton Hospital sent 16th Jan 2019 on behalf of the London South GLH for review by the GMS Cardiology Specialist Group. Only gene symbol from the Royal Brompton gene panel was provided - suggested initial gene rating and evidence for inclusion not provided with the list.

Created: 20 Feb 2019, 2:17 p.m.

Two families described in PMID: 26854927.

Created: 12 Apr 2017, 3:09 p.m.

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

Phenotypes
{Aortic aneurysm, familial thoracic 11, susceptibility to}

Publications

• 26854927