Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/172897
Title: Analysis of neurodegenerative disease-causing genes in dementia with Lewy bodies
Author: Orme, Tatiana
Hernandez, Dena
Ross, Owen A.
Kun-Rodrigues, Celia
Darwent, Lee
Shepherd, Claire E.
Parkkinen, Laura
Ansorge, Olaf
Clark, Lorraine N.
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
Deerlin, Vivianna Van
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
Keywords: Demència amb cossos de Lewy
Malalties neurodegeneratives
Lewy body dementia
Neurodegenerative Diseases
Issue Date: 29-Jan-2020
Publisher: BioMed Central
Abstract: 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.
Note: Reproducció del document publicat a: https://doi.org/10.1186/s40478-020-0879-z
It is part of: Acta Neuropathologica Communications, 2020, num. 8, p. 5
URI: http://hdl.handle.net/2445/172897
Related resource: https://doi.org/10.1186/s40478-020-0879-z
ISSN: 2051-5960
Appears in Collections:Articles publicats en revistes (Medicina)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

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