Thoracic aortic aneurysm or dissection (GMS)
Gene: CBS
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
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
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
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
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
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.
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
Publications for gene: CBS were set to 747076; 18799873; 16733360; 2041851; 23525608
Gene: cbs has been classified as Green List (High Evidence).
Phenotypes for gene: CBS were changed from Marfan syndrome to Marfan syndrome; Homocystinuria, B6-responsive and nonresponsive types, 236200
Publications for gene: CBS were set to
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