Ehlers Danlos syndrome with a likely monogenic cause
Gene: SMAD3
Note one case with a biallelic 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, 12:25 a.m. | Last Modified: 28 Jul 2021, 12:25 a.m.
Panel Version: 2.60
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: SMAD3; Suggested initial gene rating: greenCreated: 3 Apr 2019, 3:41 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.
Comment on phenotypes: included in EDS panel as Loeys-Dietz syndrome is a Heritable Connective Tissue Disorder.
Created: 26 Apr 2017, 1:32 p.m.
Comment on list classification: Green due to enough evidence in the literature
Created: 26 Apr 2017, 11:50 a.m.
Comment on publications: Added publications to support gene is involved in the disorder(s) in 3 or more unrelated casesCreated: 26 Apr 2017, 11:50 a.m.
Phenotypes for gene: SMAD3 were changed from Loeys-Dietz syndrome 3, 613795 to Loeys-Dietz syndrome 3, OMIM:613795
Source NHS GMS was added to SMAD3. 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.
SMAD3 was added to Ehlers-Danlos syndromespanel. Sources: Illumina TruGenome Clinical Sequencing Services
This gene has been classified as Green List (High Evidence).
Mode of inheritance for SMAD3 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for SMAD3 were set to 21217753;21778426;22167769
Phenotypes for SMAD3 were set to Loeys-Dietz syndrome 3, 613795
SMAD3 was created by ellenmcdonagh
SMAD3 was added to Ehlers-Danlos syndromespanel. Sources: Emory Genetics Laboratory,Expert list