Thoracic aortic aneurysm or dissection
Gene: COL5A1Review 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
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
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
130000 Classic Ehlers-Danlos syndrome; well characterised geneCreated: 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
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 TAADCreated: 19 Feb 2016, 2:53 p.m.
Comment on mode of inheritance: Ehlers-Danlos syndrome, classic type - ADCreated: 19 Feb 2016, 2:50 p.m.
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.
Publications for gene: COL5A1 were set to 26188975; 10946364; 28868310; 25845371; 239975631; 2180144; 29543232
Phenotypes for gene: COL5A1 were changed from Ehlers-Danlos syndrome vascular type; Ehlers-Danlos syndrome, classic type, 130000 to Ehlers-Danlos syndrome, classic type, OMIM:130000; Fibromuscular dysplasia, multifocal, OMIM:619329
Publications for gene: COL5A1 were set to 26188975; 10946364
Source South West GLH was added to COL5A1.
Source London South GLH was added to COL5A1. Rating Changed from Green List (high evidence) to Green List (high evidence)
Publications for COL5A1 were set to 26188975; 10946364
Phenotypes for COL5A1 were set to Ehlers-Danlos syndrome vascular type; Ehlers-Danlos syndrome, classic type, 130000
This gene has been classified as Green List (High Evidence).
This gene has been classified as Green List (High Evidence).
Mode of inheritance for COL5A1 was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for COL5A1 were set to Ehlers-Danlos syndrome vascular type; Ehlers-Danlos syndrome, classic type
COL5A1 was added to Familial thoracic aortic aneurysms and dissectionpanel. Sources: Emory Genetics Laboratory,Expert list
COL5A1 was added to Familial thoracic aortic aneurysms and dissectionpanel. Sources: Emory Genetics Laboratory,Expert list