Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

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

Orme, Tatiana ; Londos, Elisabet LU and Bras, Jose (2020) In Acta Neuropathologica Communications 8(1).
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
; and
author collaboration
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Acta Neuropathologica Communications
volume
8
issue
1
article number
5
publisher
BioMed Central (BMC)
external identifiers
  • scopus:85078689290
  • pmid:31996268
ISSN
2051-5960
DOI
10.1186/s40478-020-0879-z
language
English
LU publication?
yes
id
da230154-7cb4-4b26-b08c-0735c5c641ca
date added to LUP
2020-02-11 16:51:54
date last changed
2022-05-12 00:29:59
@article{da230154-7cb4-4b26-b08c-0735c5c641ca,
  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.}},
  author       = {{Orme, Tatiana and Londos, Elisabet and Bras, Jose}},
  issn         = {{2051-5960}},
  language     = {{eng}},
  month        = {{01}},
  number       = {{1}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{Acta Neuropathologica Communications}},
  title        = {{Analysis of neurodegenerative disease-causing genes in dementia with Lewy bodies}},
  url          = {{http://dx.doi.org/10.1186/s40478-020-0879-z}},
  doi          = {{10.1186/s40478-020-0879-z}},
  volume       = {{8}},
  year         = {{2020}},
}