Thoracic aortic aneurysm or dissection (GMS)

Gene: FKBP14

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

Submitted on behalf of the GMS Cardiology specialist group. The group has agreed that this gene should be Amber on this panel. Therefore this gene has been promoted from Red to Amber.

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 a form of EDS, uncertain if this form of the condition includes aortopathy.

Created: 2 Oct 2019, 12:30 p.m. | Last Modified: 2 Oct 2019, 12:30 p.m.

Panel Version: 0.32

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Ehlers-Danlos syndrome, kyphoscoliotic type, 2 614557

Publications

• 22265013

Green List (high evidence)

614557 Ehlers-Danlos syndrome, kyphoscoliotic type, 2 - rare aortic rupture and occasional patent ductus arteriosus, with other cardiac involvement being tricuspid and mitral valve insufficiency.

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

6 variants described on ClinVar missense and truncating: Giunta et al 2018 Genet Med 20:42 PMID:28617417 describe 17 affected patients from 15 families all are homozygous for a total of 4 different pathogenic variants. A summary of this and a previous publication show that 6/20 patients have vascular abnormalities. This publication includes one patient with coronary artery dissection, one with a dilated aorta and one with borderline aortic root diameter. Baumann et al 2012 Am J Hum Genet 90:201 PMID:22265013 describe 6 patients from 5 families who are homozygous or compound heterozygous for FKBP14 variants and have some supporting functional work in FKBP14 deficient fibroblasts. One patient has aortic rupture.

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

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Green List (high evidence)

Comment when marking as ready: Not on Sherbrooke Genomic Medicine (SGM) not-for-profit TAAD panel: http://sherbrookegenomicmedicine.ca/index.php/en/services-en/cardiogenetics-en/taad-en

Created: 19 Feb 2016, 3:01 p.m.

Not on the Inherited Cardiac Condition Genes panel for Familial aortic anuerysm reported in: Development of a Comprehensive Sequencing Assay for Inherited Cardiac Condition Genes, Pua et al, Journal of Cardiovascular Translational Research, online Feb 2016 (doi:10.​1007/​s12265-016-9673-5). The panel contains disease-causing, putatively pathogenic, research and phenocopy genes.

Created: 19 Feb 2016, 10:57 a.m.

Red List (low evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
# 614557- Ehlers-Danlos syndrome with progressive kyphoscoliosis, myopathy, and hearing loss

Publications

• PMID: 22265013