دورية أكاديمية

Analysis of neurodegenerative disease-causing genes in dementia with Lewy bodies.

التفاصيل البيبلوغرافية
العنوان: Analysis of neurodegenerative disease-causing genes in dementia with Lewy bodies.
المؤلفون: Orme, Tatiana, Hernandez, Dena, Ross, Owen A, Kun-Rodrigues, Celia, Darwent, Lee, Shepherd, Claire E, Parkkinen, Laura, Ansorge, Olaf, Clark, Lorraine, Honig, Lawrence S, Marder, Karen, Lemstra, Afina, Rogaeva, Ekaterina, St George-Hyslop, Peter, Londos, Elisabet, Zetterberg, Henrik, Morgan, Kevin, Troakes, Claire, Al-Sarraj, Safa, Lashley, Tammaryn, Holton, Janice, Compta, Yaroslau, Van Deerlin, Vivianna, Trojanowski, John Q, Serrano, Geidy E, Beach, Thomas G, Lesage, Suzanne, Galasko, Douglas, Masliah, Eliezer, Santana, Isabel, Pastor, Pau, Tienari, Pentti J, Myllykangas, Liisa, Oinas, Minna, Revesz, Tamas, Lees, Andrew, Boeve, Brad F, Petersen, Ronald C, Ferman, Tanis J, Escott-Price, Valentina, Graff-Radford, Neill, Cairns, Nigel J, Morris, John C, Pickering-Brown, Stuart, Mann, David, Halliday, Glenda, Stone, David J, Dickson, Dennis W, Hardy, John, Singleton, Andrew, Guerreiro, Rita, Bras, Jose
بيانات النشر: Springer Science and Business Media LLC
//dx.doi.org/10.1186/s40478-020-0879-z
Acta Neuropathol Commun
سنة النشر: 2020
المجموعة: Apollo - University of Cambridge Repository
مصطلحات موضوعية: Aged, 80 and over, Cerebellum, Cohort Studies, Female, Frontal Lobe, Humans, Lewy Body Disease, Male, Mutation, Neurodegenerative Diseases, Exome Sequencing
الوصف: Dementia with Lewy bodies (DLB) is a clinically heterogeneous disorder with a substantial burden on healthcare. Despite this, the genetic basis of the disorder is not well defined and its boundaries with other neurodegenerative diseases are unclear. Here, we performed whole exome sequencing of a cohort of 1118 Caucasian DLB patients, and focused on genes causative of monogenic neurodegenerative diseases. We analyzed variants in 60 genes implicated in DLB, Alzheimer's disease, Parkinson's disease, frontotemporal dementia, and atypical parkinsonian or dementia disorders, in order to determine their frequency in DLB. We focused on variants that have previously been reported as pathogenic, and also describe variants reported as pathogenic which remain of unknown clinical significance, as well as variants associated with strong risk. Rare missense variants of unknown significance were found in APP, CHCHD2, DCTN1, GRN, MAPT, NOTCH3, SQSTM1, TBK1 and TIA1. Additionally, we identified a pathogenic GRN p.Arg493* mutation, potentially adding to the diversity of phenotypes associated with this mutation. The rarity of previously reported pathogenic mutations in this cohort suggests that the genetic overlap of other neurodegenerative diseases with DLB is not substantial. Since it is now clear that genetics plays a role in DLB, these data suggest that other genetic loci play a role in this disease.
نوع الوثيقة: article in journal/newspaper
وصف الملف: Electronic; application/pdf
اللغة: English
العلاقة: https://www.repository.cam.ac.uk/handle/1810/303894Test
DOI: 10.17863/CAM.50978
الإتاحة: https://doi.org/10.17863/CAM.50978Test
https://www.repository.cam.ac.uk/handle/1810/303894Test
حقوق: Attribution 4.0 International ; https://creativecommons.org/licenses/by/4.0Test/
رقم الانضمام: edsbas.1130386F
قاعدة البيانات: BASE