Thoracic aortic aneurysm or dissection

Gene: SMAD3

Note one case with homozygous variant reported:
PMID: 32935439 - Baskin et al 2020 - first report of a LDS patient with biallelic SMAD3 variants (affecting splice site). Proband had classic Loeys-Dietz features, including dysmorphic facial features, significant scoliosis, and pectus excavatum, arachnodactyly, severe aortic root dilation, and diffuse arterial tortuosity. His parents are each heterozygous for the likely pathogenic variant and are more mildly affected.

Created: 28 Jul 2021, 12:22 a.m. | Last Modified: 28 Jul 2021, 12:22 a.m.

Panel Version: 1.121

Green List (high evidence)

Well characterised aortopathy gene; present on Wessex aortopathy and TAAD panels.

Created: 8 May 2019, 12:32 p.m.

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

Green List (high evidence)

613795 Loeys-Dietz syndrome; well characterised gene

Created: 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

Green List (high evidence)

Gene currently tested on Manchester cardiac gene panel. 95 variants listed on HGMD (accessed 29/01/2019). ClinGen Knowledge Base: definitive association with TAAD, definitive association with aneurysm-osteoarthritis syndrome (accessed 29/01/2019).

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

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

Phenotypes
Loeys Dietz syndrome, type 3 (613795)

Publications

• 21217753
• 29392890

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

Green List (high evidence)

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.

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. No. of mutations indicated in supplemental table = 9.

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

Publications

• doi:10.​1007/​s12265-016-9673-5
• 21217753