5 documents found, page 1 of 1
Rare nonsynonymous variants in SORT1 are associated with increased risk for fro...
Philtjens, Stéphanie; Van Mossevelde, Sara; van der Zee, Julie; Wauters, Eline; Dillen, Lubina; Vandenbulcke, Mathieu; Vandenberghe, RikWe investigated the genetic role of sortilin (SORT1) in frontotemporal dementia (FTD). SORT1 is the neuronal receptor for granulin, encoded by the progranulin gene (GRN), a major causal gene for inherited FTD. In Belgian cohorts of 636 FTD patients and 1066 unaffected control individuals, we identified 5 patient-only nonsynonymous rare variants in SORT1. Rare variant burden analysis showed a significant increas...
TBK1 mutation spectrum in an extended European patient cohort with frontotempor...
van der Zee, Julie; Gijselinck, Ilse; Van Mossevelde, Sara; Perrone, Federica; Dillen, Lubina; Heeman, Bavo; Bäumer, Veerle; Engelborghs, SebastiaanWe investigated the mutation spectrum of the TANK-Binding Kinase 1 (TBK1) gene and its associated phenotypic spectrum by exonic resequencing of TBK1 in a cohort of 2,538 patients with frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), or FTD plus ALS, ascertained within the European Early-Onset Dementia Consortium. We assessed pathogenicity of predicted protein-truncating mutations by measuring...
A comprehensive study of the genetic impact of rare variants in SORL1 in Europe...
Verheijen, Jan; Van den Bossche, Tobi; van der Zee, Julie; Engelborghs, Sebastiaan; Sanchez-Valle, Raquel; Lladó, Albert; Graff, CarolineThe sortilin-related receptor 1 (SORL1) gene has been associated with increased risk for Alzheimer's disease (AD). Rare genetic variants in the SORL1 gene have also been implicated in autosomal dominant early-onset AD (EOAD). Here we report a large-scale investigation of the contribution of genetic variability in SORL1 to EOAD in a European EOAD cohort. We performed massive parallel amplicon-based re-sequencing...
Rare variants in PLD3 do not affect risk for early-onset Alzheimer disease in a...
Cacace, Rita; Van den Bossche, Tobi; Engelborghs, Sebastiaan; Geerts, Nathalie; Laureys, Annelies; Dillen, Lubina; Graff, Caroline; Thonberg, HåkanRare variants in the phospholipase D3 gene (PLD3) were associated with increased risk for late-onset Alzheimer disease (LOAD). We identified a missense mutation in PLD3 in whole-genome sequence data of a patient with autopsy confirmed Alzheimer disease (AD) and onset age of 50 years. Subsequently, we sequenced PLD3 in a Belgian early-onset Alzheimer disease (EOAD) patient (N = 261) and control (N = 319) cohort,...
Redox metals and oxidative abnormalities in human prion diseases
Petersen, Robert; Siedlak, Sandra; Lee, Hyoung-Gon; Kim, Yong-Sun; Nunomura, Akihiko; Tagliavini, Fabrizio; Ghetti, Bernardino; Cras, PatrickPrion diseases are characterized by the accumulation of diffuse and aggregated plaques of protease-resistant prion protein (PrP) in the brains of affected individuals and animals. Whereas prion diseases in animals appear to be almost exclusively transmitted by infection, human prion diseases most often occur sporadically and, to a lesser extent, by inheritance or infection. In the sporadic cases (sporadic Creut...