Thoracic aortic aneurysm or dissection

Gene: CBS

Comment on list classification: Promoted from Red to Amber based on evidence provided by expert reviews.

Created: 6 Jan 2020, 11:12 a.m. | Last Modified: 6 Jan 2020, 11:12 a.m.

Panel Version: 1.110

I don't know

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 may include a cardiac/thrombosis phenotype, so overlaps with TAAD.

Created: 8 May 2019, 4:37 p.m.

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

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

Red List (low evidence)

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.

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

• PMID: 747076
• 18799873
• 16733360
• 2041851
• 23525608