The effect of NOTCH3 pathogenic variant position on CADASIL disease severity: NOTCH3 EGFr 1-6 pathogenic variant are associated with a more severe phenotype and lower survival compared with EGFr 7-34 pathogenic variant

Genetics in Medicine : Official Journal of the American College of Medical Genetics
Julie W RuttenS A J Lesnik Oberstein

Abstract

CADASIL is a small-vessel disease caused by a cysteine-altering pathogenic variant in one of the 34 epidermal growth factor-like repeat (EGFr) domains of the NOTCH3 protein. We recently found that pathogenic variant in EGFr domains 7-34 have an unexpectedly high frequency in the general population (1:300). We hypothesized that EGFr 7-34 pathogenic variant more frequently cause a much milder phenotype, thereby explaining an important part of CADASIL disease variability. Age at first stroke, survival and white matter hyperintensity volume were compared between 664 CADASIL patients with either a NOTCH3 EGFr 1-6 pathogenic variant or an EGFr 7-34 pathogenic variant. The frequencies of NOTCH3 EGFr 1-6 and EGFr 7-34 pathogenic variant were compared between individuals in the genome  Aggregation Database and CADASIL patients. CADASIL patients with an EGFr 1-6 pathogenic variant have a 12-year earlier onset of stroke than those with an EGFr 7-34 pathogenic variant, lower survival, and higher white matter hyperintensity volumes. Among diagnosed CADASIL patients, 70% have an EGFr 1-6 pathogenic variant, whereas EGFr 7-34 pathogenic variant strongly predominate in the population. NOTCH3 pathogenic variant position is the most important de...Continue Reading

References

Aug 26, 1998·Neurology·H ChabriatM G Bousser
Nov 18, 1998·Annals of Neurology·M DichgansT Gasser
Sep 26, 2001·Neurology·S A Lesnik ObersteinUNKNOWN Dutch CADASIL Research Group
Jul 24, 2002·Neurology·J F Arboleda-VelasquezK S Kosik
Sep 15, 2004·Brain : a Journal of Neurology·Christian OpherkMartin Dichgans
Nov 21, 2007·Journal of the Neurological Sciences·Francesca PesciniLeonardo Pantoni
Mar 19, 2009·Brain : a Journal of Neurology·Marie Monet-LeprêtreAnne Joutel
Jun 23, 2009·Lancet Neurology·Hugues ChabriatMarie-Germaine Bousser
May 11, 2011·Proceedings of the National Academy of Sciences of the United States of America·Joseph F Arboleda-VelasquezSpyros Artavanis-Tsakonas
Mar 1, 2014·Stroke; a Journal of Cerebral Circulation·Christian OpherkMartin Dichgans
May 3, 2014·Stroke; a Journal of Cerebral Circulation·Walter N KernanUNKNOWN American Heart Association Stroke Council, Council on Cardiovascular and Stroke Nursing, Council on Clinical Cardiology, and
May 23, 2014·Expert Review of Molecular Diagnostics·Julie W RuttenSaskia A J Lesnik Oberstein
Apr 30, 2015·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Benno GesierichMichael Ewers
Aug 19, 2016·Nature·Monkol LekUNKNOWN Exome Aggregation Consortium
Nov 16, 2016·Annals of Clinical and Translational Neurology·Julie W RuttenSaskia A J Lesnik Oberstein

❮ Previous
Next ❯

Citations

Sep 11, 2019·Wiley Interdisciplinary Reviews. Developmental Biology·Diana M HoAngeliki Louvi
Mar 21, 2020·European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies·M MancusoH S Markus
Mar 27, 2020·Biomolecules·Samira Hosseini-Alghaderi, Martin Baron
Apr 30, 2020·European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies·H ChabriatM G Bousser
Apr 12, 2020·Journal of Human Genetics·Mao MukaiToshiki Mizuno
Aug 1, 2020·Neurology·Julie W RuttenSaskia A J Lesnik Oberstein
Aug 5, 2020·Neurology·Peter Hedera
May 28, 2020·Frontiers in Aging Neuroscience·Toshiki MizunoTakashi Koizumi
Apr 23, 2020·Journal of Neurology·A BersanoH S Markus
Nov 23, 2019·Stroke; a Journal of Cerebral Circulation·Eric JouventHugues Chabriat
Aug 20, 2019·Annual Review of Pharmacology and Toxicology·Anne Joutel
Oct 6, 2020·Frontiers in Neurology·Ayesha KhanRamin Zand
Nov 10, 2020·Stroke; a Journal of Cerebral Circulation·Raj N Kalaria, Steven J Kittner
Nov 10, 2020·Stroke; a Journal of Cerebral Circulation·Remco J HackRamin Zand
Nov 21, 2020·Journal of Neurology·Maria Rosário AlmeidaGustavo Cordeiro Santo
Jan 15, 2021·Journal of Cell Science·Oscar M J A StassenCecilia M Sahlgren
Feb 19, 2021·Journal of Stroke·Gido GravesteijnSaskia A J Lesnik Oberstein
Apr 26, 2021·The American Journal of Pathology·Dorothee Schoemaker, Joseph F Arboleda-Velasquez
Jun 3, 2021·Journal of Personalized Medicine·Stefania ZampattiEmiliano Giardina
Jul 25, 2021·International Journal of Molecular Sciences·Elena MuiñoAdrià Arboix
Jan 2, 2021·Seminars in Cell & Developmental Biology·Arunima Kapoor, Daniel A Nation
Jul 24, 2021·Neuropathology and Applied Neurobiology·Gido GravesteijnSaskia A J Lesnik Oberstein
Aug 18, 2021·Stroke; a Journal of Cerebral Circulation·Stéphanie GueyHugues Chabriat
Jun 19, 2019·Neuro-degenerative Diseases·Xiangyu ChenLamei Yuan
Dec 2, 2021·Neurogenetics·Maria Rosário AlmeidaGustavo Santo
Jul 10, 2020·Neurology. Clinical Practice·Laura Donker KaatSaskia A M J Lesnik Oberstein

❮ Previous
Next ❯

Software Mentioned

GnomAD

Related Concepts

Related Feeds

Acute Stroke

A stroke occurs when blood supply to the brain is interrupted depriving the brain of oxygen and nutrients. This feed focuses cerebrovascular accidents including ischemic and paralytic stroke.

© 2022 Meta ULC. All rights reserved