Thoracic aortic aneurysm and dissection

Gene: CBS

Green List (high evidence)

CBS (cystathionine-beta-synthase)
EnsemblGeneIds (GRCh38): ENSG00000160200
EnsemblGeneIds (GRCh37): ENSG00000160200
OMIM: 613381, Gene2Phenotype
CBS is in 14 panels

8 reviews

James Eden (Manchester)

I don't know

Aortic root dilation appears to be a rare symptom of homocystinuria, uncertain whether this sufficient for inclusion in the TAAD panel. Gene is not currently tested in Manchester TAAD panel.
Created: 25 Sep 2019, 9 a.m. | Last Modified: 25 Sep 2019, 9:01 a.m.
Panel Version: 0.30

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Homocystinuria, B6-responsive and nonresponsive types 236200; Thrombosis, hyperhomocysteinemic 236200

Publications

Matthew Edwards (Clinical Genetics & Genomics Lab, Royal Brompton & Harefield NHS Trust)

I don't know

Not currently on CGGL Royal Brompton FTAA panel. Appreciate overlap with symptoms, however does existence on this panel depend on likelihood of ever having a referral with aortopathy without other symptoms?
Created: 18 Sep 2019, 2:13 p.m. | Last Modified: 18 Sep 2019, 2:13 p.m.
Panel Version: 0.30

Ivone Leong (Genomics England Curator)

Green List (high evidence)

Submitted on behalf of the GMS Cardiology specialist group. The group has agreed that this gene should be Green on this panel.
Created: 18 Nov 2019, 4:33 p.m. | Last Modified: 18 Nov 2019, 4:33 p.m.
Panel Version: 0.35
Comment on list classification: Promoted from red to green based on evidence provided by expert reviews.
Created: 12 Sep 2019, 1:51 p.m. | Last Modified: 12 Sep 2019, 1:51 p.m.
Panel Version: 0.28

Alison Callaway (Wessex Regional Genetics Laboratory, Salisbury NHS Foundation Trust)

Green List (high evidence)

On Wessex aortopathy panel. To date, only one case run on this panel has been identified to have two CBS variants; they were primarily referred with homocystinuria and left ventricular hypertrophy (and CBS was suspected as the causative gene by the referrer).
CBS is associated with homocystinuria which includes a cardiac/thrombosis phenotype, so overlaps with TAAD (OMIM #236200).
Created: 29 Aug 2019, 11:32 a.m. | Last Modified: 29 Aug 2019, 11:32 a.m.
Panel Version: 0.5

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
HOMOCYSTINURIA DUE TO CYSTATHIONINE BETA-SYNTHASE DEFICIENCY

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

Rebecca Whittington (South West GLH)

Green List (high evidence)

236200 Homocystinuria - clinical synopsis for homocystinuria on OMIM includes tall stature, ectopia lentis, myopia, mitral valve prolapse, pectus, kyphoscoliosis and arachnodactyly - phenotypic overlap with Marfan/EDS/LDS syndromic features. Gene is green in EDS panel.
Created: 25 Mar 2019, 4:30 p.m.
Narayanan et al (Int J Physiol Pathophysiol Pharmacol 2013:32 PMID:23525608) - Homocystinuria may present with aortic aneurysm. Decreased expression of Collagens I and IV was observed in CBS+/- mice, analagous to changes seen in TAAD. Gaustadnes et al (HUMAN MUTATION 20:117 2002 PMID:12124992) describes 36 patients with homocystinuria and two variants in CBS. Dislocated lenses and Marfaniod features were reported in many of these patients, with aortic root dilation in one.
Created: 25 Mar 2019, 4:27 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

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

David Parry (University of Edinburgh)

Red List (low evidence)

Ellen McDonagh (Genomics England Curator)

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, 10:53 a.m.

Matina Prapa (Genomics England Curator)

Red List (low evidence)

Not classically related to TAAD. A few case reports in the literature of (non-thoracic) aneurysm formation. Plausible role of epigenetics in regulation of gene expression involved in aortopathy and homocysteine metabolism (see ref above). No familial cases found.
Created: 11 Feb 2016, 2:50 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
# 236200- Homocystinuria, B6-responsive and nonresponsive types; #236200- Thrombosis, hyperhomocysteinemic

Publications

History Filter Activity

19 Nov 2019, Gel status: 3

Set publications

Ivone Leong (Genomics England Curator)

Publications for gene: CBS were set to 747076; 18799873; 16733360; 2041851; 23525608

12 Sep 2019, Gel status: 3

Entity classified by Genomics England curator

Ivone Leong (Genomics England Curator)

Gene: cbs has been classified as Green List (High Evidence).

11 Sep 2019, Gel status: 1

Set Phenotypes

Ivone Leong (Genomics England Curator)

Phenotypes for gene: CBS were changed from Marfan syndrome to Marfan syndrome; Homocystinuria, B6-responsive and nonresponsive types, 236200

11 Sep 2019, Gel status: 1

Set publications

Ivone Leong (Genomics England Curator)

Publications for gene: CBS were set to

18 Apr 2019, Gel status: 1

Created, Added New Source, Set mode of inheritance, Set Phenotypes

Ellen McDonagh (Genomics England Curator)

gene: CBS was added gene: CBS was added to GMS FTAAD placeholder panel. Sources: South West GLH,Expert Review Red Mode of inheritance for gene: CBS was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: CBS were set to Marfan syndrome