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Analysis of neurodegenerative disease-causing genes in dementia with Lewy bodies
- Source :
- Dipòsit Digital de la UB, Universidad de Barcelona, Acta Neuropathologica Communications, Vol 8, Iss 1, Pp 1-11 (2020), 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 Communinications, vol. 8, no. 1, 5, pp. 5 . https://doi.org/10.1186/s40478-020-0879-z, Acta Neuropathologica Communications, Acta Neuropathologica Communinications, 8(1):5. BioMed Central
- Publication Year :
- 2020
- Publisher :
- Springer Science and Business Media LLC, 2020.
-
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.
- Subjects :
- Male
ALPHA-SYNUCLEIN
Disease
3124 Neurology and psychiatry
lcsh:RC346-429
Cohort Studies
chemistry.chemical_compound
0302 clinical medicine
Cerebellum
Missense mutation
NOTCH3 MUTATIONS
Exome sequencing
Aged, 80 and over
Genetics
0303 health sciences
Malalties neurodegeneratives
Demència amb cossos de Lewy
Neurodegenerative Diseases
Frontal Lobe
3. Good health
ALZHEIMERS-DISEASE
GENOME
Medical genetics
Female
Lewy body dementia
PAGETS-DISEASE
Frontotemporal dementia
Lewy Body Disease
medicine.medical_specialty
APOLIPOPROTEIN-E
Pathology and Forensic Medicine
03 medical and health sciences
Cellular and Molecular Neuroscience
Exome Sequencing
mental disorders
medicine
Humans
PROGRANULIN
lcsh:Neurology. Diseases of the nervous system
Aged
030304 developmental biology
Alpha-synuclein
business.industry
Dementia with Lewy bodies
Research
3112 Neurosciences
FRONTOTEMPORAL DEMENTIA
medicine.disease
nervous system diseases
DCTN1
chemistry
Mutation
BODY DISEASE
Neurology (clinical)
TAU
business
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 20515960
- Volume :
- 8
- Database :
- OpenAIRE
- Journal :
- Acta Neuropathologica Communications
- Accession number :
- edsair.doi.dedup.....4e9c499de6a3910aefa11634062d5191