Ehlers Danlos syndromes

Gene: SMAD4

No list

SMAD4 (SMAD family member 4)
EnsemblGeneIds (GRCh38): ENSG00000141646
EnsemblGeneIds (GRCh37): ENSG00000141646
OMIM: 600993, Gene2Phenotype
SMAD4 is in 26 panels

5 reviews

Eleanor Williams (Genomics England Curator)

I don't know

Comment on list classification: Following discussion in the GMS musculoskeletal specialist test group Webex on 2019-06-04, it was decided to remove this gene from the panel as there is not enough overlap with the EDS phenotype.
Created: 11 Jun 2019, 11:09 a.m.
This gene was part of an initial gene list collated by Duncan Baker, Sheffield Diagnostic Genetics Service, January 2019 on behalf of the GMS Musculoskeletal Specialist Group; Gene symbol submitted: SMAD4; Suggested initial gene rating: red
Created: 3 Apr 2019, 3:41 p.m.

Duncan Baker (Sheffield Genetics)

Red List (low evidence)

D/w Dr Diana Johnson, not enough overlap with EDS features.
e.g. PMID: 24525918: Seven of the 34 individuals in the study (21%), from five separate families, had documented evidence of connective tissue findings.
Created: 24 Jan 2019, 11:51 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
juvenile polyposis syndrome (JP) and hereditary hemorrhagic telangiectasia (HHT); ~20% with connective tissue features.

Angela Brady (Nhs)

Green List (high evidence)

Neeti Ghali (NWTRGS, Northwick Park Hospital)

Green List (high evidence)

Louise Daugherty (Genomics England Curator)

Green List (high evidence)

In consultation with the clinical team it was decided to include this gene, due to the clinical overlap of the phenotype with EDS
Created: 24 May 2017, 1:11 p.m.
Refer to clinical team for further discussion on wether we should include this gene on the EDS panel. There is clinical overlap between EDS and other Heritable Connective Tissue Disorders.
Created: 28 Apr 2017, 11:50 a.m.
SMAD4 is part of the TGFβ pathway with integral role of the latter in Thoracic Aortic Aneurysms and Aortic Dissections (TAAD), including Marfan and Loeys-Dietz syndrome.
Created: 26 Apr 2017, 12:29 p.m.

History Filter Activity

26 Feb 2021, Gel status: 0

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag curated_removed tag was added to gene: SMAD4.

11 Jun 2019, Gel status: 0

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: smad4 has been removed from the panel.

15 May 2019, Gel status: 4

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: SMAD4 were changed from Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, 175050 to Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, 175050; juvenile polyposis syndrome (JP) and hereditary hemorrhagic telangiectasia (HHT); ~20% with connective tissue features.

13 Mar 2019, Gel status: 3

Added New Source, Status Update

Eleanor Williams (Genomics England Curator)

Source NHS GMS was added to SMAD4. Rating Changed from Green List (high evidence) to Green List (high evidence)

25 Jul 2017, Gel status: 4

panel promoted to version 1

Louise Daugherty (Genomics England Curator)

25 July 2017 Panel reviews were assessed, and panel was revised according to reviews and further curation.

26 Apr 2017, Gel status: 4

Upload gene information

Louise Daugherty (Genomics England Curator)

SMAD4 was added to Ehlers-Danlos syndromespanel. Sources: Illumina TruGenome Clinical Sequencing Services,Radboud University Medical Center, Nijmegen

26 Apr 2017, Gel status: 4

Gene classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

26 Apr 2017, Gel status: 0

Set publications

Louise Daugherty (Genomics England Curator)

Publications for SMAD4 were set to 26699655; 23239472; 25931195;21465659

26 Apr 2017, Gel status: 0

Set Mode of Inheritance

Louise Daugherty (Genomics England Curator)

Mode of inheritance for SMAD4 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

26 Apr 2017, Gel status: 0

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for SMAD4 were set to Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, 175050

26 Apr 2017, Gel status: 0

Set publications

Louise Daugherty (Genomics England Curator)

Publications for SMAD4 were set to 26699655; 23239472;25931195

26 Apr 2017, Gel status: 0

Set publications

Louise Daugherty (Genomics England Curator)

Publications for SMAD4 were set to 26699655; 23239472;25931195

24 Jan 2017, Gel status: 0

Added New Source

Ellen McDonagh (Genomics England Curator)

SMAD4 was added to Ehlers-Danlos syndromespanel. Sources: Expert list

24 Jan 2017, Gel status: 0

Created

Ellen McDonagh (Genomics England Curator)

SMAD4 was created by ellenmcdonagh