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

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http://hdl.handle.net/10138/313374

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Orme , T , Hernandez , D , Ross , O A , Kun-Rodrigues , C , Darwent , L , Shepherd , C E , Parkkinen , L , Ansorge , O , Clark , L , Honig , L S , Marder , K , Lemstra , A , Rogaeva , E , St. George-Hyslop , P , Londos , E , Zetterberg , H , Morgan , K , Troakes , C , Al-Sarraj , S , Lashley , T , Holton , J , Compta , Y , Van Deerlin , V , Trojanowski , J Q , Serrano , G E , Beach , T G , Lesage , S , Galasko , D , Masliah , E , Santana , I , Pastor , P , Tienari , P J , Myllykangas , L , Oinas , M , Revesz , T , Lees , A , Boeve , B F , Petersen , R C , Ferman , T J , Escott-Price , V , Graff-Radford , N , Cairns , N J , Morris , J C , Pickering-Brown , S , Mann , D , Halliday , G , Stone , D J , Dickson , D W , Hardy , J , Singleton , A , Guerreiro , R & Bras , J 2020 , ' Analysis of neurodegenerative disease-causing genes in dementia with Lewy bodies ' , Acta Neuropathologica Communications , vol. 8 , no. 1 , 5 . https://doi.org/10.1186/s40478-020-0879-z

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; 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
Contributor: University of Helsinki, HUS Neurocenter
University of Helsinki, HUSLAB
University of Helsinki, Clinicum
Date: 2020-01-29
Language: eng
Number of pages: 11
Belongs to series: Acta Neuropathologica Communications
ISSN: 2051-5960
URI: http://hdl.handle.net/10138/313374
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.
Subject: FRONTOTEMPORAL DEMENTIA
ALPHA-SYNUCLEIN
ALZHEIMERS-DISEASE
NOTCH3 MUTATIONS
APOLIPOPROTEIN-E
PAGETS-DISEASE
BODY DISEASE
PROGRANULIN
GENOME
TAU
3112 Neurosciences
3124 Neurology and psychiatry
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