Ehlers Danlos syndrome with a likely monogenic cause
Gene: SMAD4
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: redCreated: 3 Apr 2019, 3:41 p.m.
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.
In consultation with the clinical team it was decided to include this gene, due to the clinical overlap of the phenotype with EDSCreated: 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.
Tag curated_removed tag was added to gene: SMAD4.
Gene: smad4 has been removed from the panel.
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.
Source NHS GMS was added to SMAD4. Rating Changed from Green List (high evidence) to Green List (high evidence)
25 July 2017 Panel reviews were assessed, and panel was revised according to reviews and further curation.
SMAD4 was added to Ehlers-Danlos syndromespanel. Sources: Illumina TruGenome Clinical Sequencing Services,Radboud University Medical Center, Nijmegen
This gene has been classified as Green List (High Evidence).
Publications for SMAD4 were set to 26699655; 23239472; 25931195;21465659
Mode of inheritance for SMAD4 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for SMAD4 were set to Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, 175050
Publications for SMAD4 were set to 26699655; 23239472;25931195
Publications for SMAD4 were set to 26699655; 23239472;25931195
SMAD4 was added to Ehlers-Danlos syndromespanel. Sources: Expert list
SMAD4 was created by ellenmcdonagh