Thoracic aortic aneurysm or dissection

Gene: COL5A1

Review submitted by Zornitza Stark (Australian Genomics) to the Thoracic aortic aneurysm and dissection (Version 1.12) panel:

"New disease entity: Multifocal fibromuscular dysplasia (FMDMF) is characterized histologically by medial fibroplasia and angiographically by multiple arterial stenoses with intervening mural dilations. Arterial tortuosity, macroaneurysms, dissections, and rupture may occur. 4 unrelated individuals reported, but all had the same variant, p.Gly514Ser, and haplotype analysis was consistent with founder effect. Further rare missense variants were identified in a cohort, although limited information available. Association with classic EDS well established.
Zornitza Stark (Australian Genomics), 11 Jun 2021"

Created: 16 Jun 2021, 2:22 p.m. | Last Modified: 16 Jun 2021, 2:22 p.m.

Panel Version: 1.117

Publications

• 32938213

I don't know

Gene not currently tested on Manchester cardiac gene panel. 191 variants listed on HGMD (accessed 24/09/2019).

Created: 24 Sep 2019, 2:03 p.m. | Last Modified: 24 Sep 2019, 2:03 p.m.

Panel Version: 1.93

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

Phenotypes
Ehlers-Danlos syndrome, classic type, 1 130000

Publications

• 28868310
• 25845371
• 239975631
• 2180144
• 29543232

I don't know

Associated with EDS, which overlaps with TAAD.
Present on Wessex aortopathy panel, but no pathogenic or likely pathogenic variants have been detected in patients referred specifically for aortopathy (without having features of EDS).

Created: 8 May 2019, 1:32 p.m.

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

Green List (high evidence)

130000 Classic Ehlers-Danlos syndrome; well characterised gene

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

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

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

Green List (high evidence)

COL5A1 is on this panel for syndromic TAAD: patients with syndromic thoracic aortic aneurysm suffer from conditions including Ehlers-Danlos syndrome (EDS). PMID:26188975 perform WES in 102 TAAD patients using a 21-gene panel including COL1A1, COL1A2, COL5A1 and COL5A2. 1 patient had suspicious variants of unknown significance in COL5A1. 1 patient had known deleterious variant in COL5A1.

Created: 29 Jun 2017, 11:36 a.m.

Comment when marking as ready: Definite disease gene for Ehlers-Danlos syndrome, overlap with TAAD

Created: 19 Feb 2016, 2:53 p.m.

Comment on mode of inheritance: Ehlers-Danlos syndrome, classic type - AD

Created: 19 Feb 2016, 2:50 p.m.

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.

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, 10:55 a.m.

Low frequency of COL5A1 mutations in TAAD (PMID: 26188975)

Created: 12 Feb 2016, 11:32 a.m.

Phenotypes
#130000- Ehlers-Danlos syndrome, classic type

Publications

• PMID: 10946364
• 26188975