Thoracic aortic aneurysm and dissection

Gene: SMAD3

Green List (high evidence)

SMAD3 (SMAD family member 3)
EnsemblGeneIds (GRCh38): ENSG00000166949
EnsemblGeneIds (GRCh37): ENSG00000166949
OMIM: 603109, Gene2Phenotype
SMAD3 is in 16 panels

9 reviews

Eleanor Williams (Genomics England Curator)

Note one case with homozygous variants 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, 12:21 a.m. | Last Modified: 28 Jul 2021, 12:21 a.m.
Panel Version: 1.15

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

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

Green List (high evidence)

On CGGL Royal Brompton panel. Several pathogenic variants reported. Strongly associated with FTAAD.
Created: 18 Sep 2019, 2:52 p.m. | Last Modified: 18 Sep 2019, 2:52 p.m.
Panel Version: 0.30

Phenotypes
OMIM: 613795 Loeys-Dietz syndrome type 3

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

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

Green List (high evidence)

Well characterised aortopathy gene (LDS type 3 OMIM#613795); present on Wessex aortopathy and TAAD panels.
Created: 29 Aug 2019, 2:27 p.m. | Last Modified: 29 Aug 2019, 2:27 p.m.
Panel Version: 0.5

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Loeys-Dietz syndrome

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

Rebecca Whittington (South West GLH)

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

James Eden (Manchester)

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

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

David Parry (University of Edinburgh)

Green List (high evidence)

Nick Camm (NHS)

Green List (high evidence)

Ellen McDonagh (Genomics England Curator)

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

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • North West GLH
  • South West GLH
  • London South GLH
  • Expert Review Green
  • South West GLH
  • London South GLH
  • North West GLH
Phenotypes
  • Loeys Dietz syndrome, type 3 (613795)
  • Loeys Dietz syndrome, type 3, 613795
OMIM
603109
Clinvar variants
Variants in SMAD3
Penetrance
None
Publications
Panels with this gene

History Filter Activity

9 Sep 2019, Gel status: 3

Set publications

Ivone Leong (Genomics England Curator)

Publications for gene: SMAD3 were set to

18 Apr 2019, Gel status: 4

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

Ellen McDonagh (Genomics England Curator)

gene: SMAD3 was added gene: SMAD3 was added to GMS FTAAD placeholder panel. Sources: Expert Review Green,London South GLH,South West GLH,North West GLH Mode of inheritance for gene: SMAD3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: SMAD3 were set to Loeys Dietz syndrome, type 3 (613795); Loeys Dietz syndrome, type 3, 613795