Thoracic aortic aneurysm or dissection (GMS)

Gene: SKI

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

Green List (high evidence)

On CGGL Royal Brompton panel. Shprintzen-Goldberg syndrome includes aortic dilatation .Good evidence for FTAAd panel inclusion

Created: 18 Sep 2019, 2:47 p.m. | Last Modified: 18 Sep 2019, 2:47 p.m.

Panel Version: 0.30

Phenotypes
Shprintzen-Goldberg syndrome

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

Green List (high evidence)

182212 Shprintzen-Goldberg syndrome - syndromic CTD including aortic root dilation

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

Doyle et al 2012 Nat Genet 44:1249 PMID:23023332 characterise several missense variants which are mostly de-novo and cluster in the SMAD2/3 binding domain and Dachshund-homology domain essential for co-repressor recrutiment. Functional analysis showed loss of repression of TGF-B signalling cascades in patient fibroblasts heterozygous for variants.

Created: 25 Mar 2019, 4:27 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)

Gene currently tested on Manchester cardiac gene panel. 24 variants listed on HGMD (accessed 29/01/2019). ClinGen Knowledge Base: definitive association with Shprintzen-Goldberg syndrome, which includes aortic dilatation (accessed 29/01/2019).

Created: 14 Feb 2019, 1:38 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Shprintzen-Goldberg syndrome (182212)

Publications

• 23023332

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

Green List (high evidence)

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

Phenotypes
Shprintzen-Goldberg Craniosynostosis Syndrome, 182212

Green List (high evidence)

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 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, and it is unclear from the publication whether this gene falls into the disease-causing category.

Created: 19 Feb 2016, 10:50 a.m.

Comment on mode of inheritance: Monallelic confirmed in G2P. Not on the imprinting gene list.

Created: 1 Feb 2016, 12:03 p.m.

Comment on list classification: Two reviewers agree this should be on the green list. Confirmed DD gene.

Created: 1 Feb 2016, 12:03 p.m.