Thoracic aortic aneurysm or dissectionGene: NOTCH1
616028 Adams-Oliver syndrome - vascular abnormalities with congenital heart defects and limb abnormalities; 109730 Aortic valve disease - BAV
Created: 25 Mar 2019, 4:30 p.m.
Meester et al 2018 Hum Mutat 39:1246 PMID:29924900 Characterisation of variants in Adams-Oliver syndrome missense, nonsense splice and frameshift variants either novel to this publication or also published elsewhere. Multiple variants classified pathogenic/likely pathogenic using ACMG criteria and gnomAD population data using criteria which appear to be stringent. Southgate et al 2015 Circ Cardiovasc Genet 8:572 PMID:25963545 show segregation of NOTCH1 variants in 4 families and de-novo in 3 families and reduction of mRNA levels implying NMD. Both publications list cardiac phenotypes including BAV, co-arctation of the aorta, aortic regurgitation, aortic stenosis and VSD.
Created: 25 Mar 2019, 4:27 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Variants in this GENE are reported as part of current diagnostic practice
PMID:16729972 report 2 sporadic BAV patients with NOTCH1 variations and ascending aortic aneurysm in both.
Created: 29 Jun 2017, 12:16 p.m.
PMID:26820064 (2016) screened NOTCH1 in 428 nonsyndromic probands with left-sided congenital heart disease- Thoracic aortic aneurysms (TAAs) and NOTCH1 mutations occurred in 6 cases.
Created: 29 Jun 2017, 12:16 p.m.
Comment on list classification: Adams Oliver syndrome, PMID: 25132448
Created: 19 Feb 2016, 3:08 p.m.
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. One mutation is indicated in the supplemental table in this gene.
Created: 19 Feb 2016, 11 a.m.
Comment when marking as ready: 1 reviewer marked green. Promoted as ready due to significant association with familial bicuspid aortic valve disease and concomitant thoracic aortic aneurysm formation.
Created: 2 Feb 2016, 2:40 p.m.
Comment on publications: Bicuspid aortic valve (BAV) disease association with familial thoracic aortic aneurysm (TAA)- two entities considered as disease spectrum of a common developmental defect. NOTCH1 mutations found in familial calcific BAV disease with concomitant TAA.
Created: 2 Feb 2016, 2:37 p.m.
Source South West GLH was added to NOTCH1.
Source London South GLH was added to NOTCH1. Rating Changed from Green List (high evidence) to Green List (high evidence)
Publications for NOTCH1 were set to 16025100; 23102684; 17662764; 26820064; 16729972
Phenotypes for NOTCH1 were set to Aortic valve disease 1, 109730
Publications for NOTCH1 were set to 16025100; 23102684; 17662764; 26820064
This gene has been classified as Green List (High Evidence).
This proposed gene was validated and added to this panel
This gene has been removed from the panel.
Publications for NOTCH1 were set to PMID: 16025100 PMID: 23102684 PMID: 17662764
Phenotypes for NOTCH1 were set to #109730 - AORTIC VALVE DISEASE BICUSPID AORTIC VALVE
NOTCH1 was added to Familial Thoracic Aortic Aneurysm Diseasepanel. Sources: UKGTN