Ehlers Danlos syndrome with a likely monogenic cause
Gene: NOTCH1Comment on phenotypes: Previous phenotypes:
Connective Tissue Disorders;Aortic valve disease 1, 109730;Familial thoracic aortic aneurysm;Bicuspid, or bicommissural, aortic valve (BAV)Created: 18 Mar 2021, 2:31 p.m. | Last Modified: 18 Mar 2021, 2:31 p.m.
Panel Version: 2.56
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: NOTCH1; Suggested initial gene rating: redCreated: 3 Apr 2019, 3:41 p.m.
Following discussion with Dr Diana Johnson - rate redCreated: 3 Apr 2019, 3:44 p.m.
No found any pathogenic mutations in service history. Phenotype not overlapping with EDS.Created: 24 Jan 2019, noon
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Bicuspid, or bicommissural, aortic valve (BAV)
Variants in this GENE are reported as part of current diagnostic practice
There is a clear gene-disease association (BAV) but in view of the relatively discrete vascular phenotype, this gene would be best placed on the FTAAD panel rather than as a differential diagnosis for those with connective tissue disease. Those with a vascular phenotype in addition would be offered the FTAAD panel in addition. D/W Neeti Ghali, EDS Specialist Clinic who is in agreement.Created: 25 Jul 2017, 1:01 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Comment on list classification: Changed from Green to Amber based due to the relatively discrete vascular phenotypeCreated: 25 Jul 2017, 12:59 p.m.
Associated with FTAA. Review from EDS National Diagnostic Service North West London Hospital NHS Trust: Dr Angela Brady FRCP PhD, Consultant Clinical Geneticist; Dr Neeti Ghali MBChB MD, Consultant Clinical Geneticist; Dr Fleur S van Dijk MD PhD, Consultant.Created: 7 Jul 2017, 6:29 p.m.
Phenotypes for gene: NOTCH1 were changed from Connective Tissue Disorders; Aortic valve disease 1, 109730; Familial thoracic aortic aneurysm; Bicuspid, or bicommissural, aortic valve (BAV) to connective tissue disease, MONDO:0003900
Phenotypes for gene: NOTCH1 were changed from Connective Tissue Disorders; Aortic valve disease 1, 109730; Familial thoracic aortic aneurysm to Connective Tissue Disorders; Aortic valve disease 1, 109730; Familial thoracic aortic aneurysm; Bicuspid, or bicommissural, aortic valve (BAV)
Source NHS GMS was added to NOTCH1.
25 July 2017 Panel reviews were assessed, and panel was revised according to reviews and further curation.
This gene has been classified as Amber List (Moderate Evidence).
This gene has been classified as Green List (High Evidence).
Phenotypes for NOTCH1 were set to Connective Tissue Disorders; Aortic valve disease 1, 109730; Familial thoracic aortic aneurysm
Publications for NOTCH1 were set to 17676603;26820064; 16729972
Phenotypes for NOTCH1 were set to Connective Tissue Disorders; Aortic valve disease 1, 109730
Publications for NOTCH1 were set to 26820064; 16729972
Mode of inheritance for NOTCH1 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for NOTCH1 were set to Connective Tissue Disorders;Adams-Oliver syndrome 5, 616028
NOTCH1 was created by ellenmcdonagh
NOTCH1 was added to Ehlers-Danlos syndromespanel. Sources: Expert list,Emory Genetics Laboratory