Genetic screen in a large series of patients with primary progressive aphasia.
C9orf72
GRN
Genetics
Primary progressive aphasia
TARDBP
Journal
Alzheimer's & dementia : the journal of the Alzheimer's Association
ISSN: 1552-5279
Titre abrégé: Alzheimers Dement
Pays: United States
ID NLM: 101231978
Informations de publication
Date de publication:
04 2019
04 2019
Historique:
received:
22
03
2018
revised:
05
10
2018
accepted:
30
10
2018
pubmed:
2
1
2019
medline:
28
4
2020
entrez:
2
1
2019
Statut:
ppublish
Résumé
Primary progressive aphasia (PPA) is a neurological syndrome, associated with both frontotemporal dementia and Alzheimer's disease, in which progressive language impairment emerges as the most salient clinical feature during the initial stages of disease. We screened the main genes associated with Alzheimer's disease and frontotemporal dementia for pathogenic and risk variants in a cohort of 403 PPA cases. In this case series study, 14 (3.5%) cases carried (likely) pathogenic variants: four C9orf72 expansions, nine GRN, and one TARDBP mutation. Rare risk variants, TREM2 R47H and MAPT A152T, were associated with a three- to seven-fold increase in risk for PPA. Our results show that while pathogenic variants within the most common dementia genes were rarely associated with PPA, these were found almost exclusively in GRN and C9orf72, suggesting that PPA is more TDP43- than tau-related in our series. This is consistent with the finding that PPA frequency in dominantly inherited dementias is the highest in kindreds with GRN variants.
Identifiants
pubmed: 30599136
pii: S1552-5260(18)33604-5
doi: 10.1016/j.jalz.2018.10.009
pmc: PMC6480353
mid: NIHMS1008100
pii:
doi:
Substances chimiques
C9orf72 Protein
0
C9orf72 protein, human
0
DNA-Binding Proteins
0
GRN protein, human
0
Progranulins
0
TARDBP protein, human
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
553-560Subventions
Organisme : NIA NIH HHS
ID : P30 AG013854
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH061675
Pays : United States
Organisme : NIA NIH HHS
ID : RC1 AG035610
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG056258
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG023501
Pays : United States
Organisme : NIDCD NIH HHS
ID : R01 DC008552
Pays : United States
Organisme : NIA NIH HHS
ID : U24 AG021886
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG052943
Pays : United States
Organisme : NIA NIH HHS
ID : K23 AG048291
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH067257
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH060870
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS075075
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH059571
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH059565
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG019724
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH059587
Pays : United States
Organisme : NINDS NIH HHS
ID : R56 NS050915
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS050915
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH059586
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH059566
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH059588
Pays : United States
Organisme : NIDCD NIH HHS
ID : K24 DC015544
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG026938
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH060879
Pays : United States
Informations de copyright
Copyright © 2019 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
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