Related Experiment Video
Updated: Feb 13, 2026

Detection of Rare Genomic Variants from Pooled Sequencing Using SPLINTER
Published on: June 23, 2012
Rare nonsynonymous variants in SORT1 are associated with increased risk for frontotemporal dementia
Stéphanie Philtjens1, Sara Van Mossevelde2, Julie van der Zee1
1Neurodegenerative Brain Diseases Group, Center for Molecular Neurology VIB, Antwerp, Belgium; Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
Abstract:
We 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 increase in rare coding variants in patients compared to control individuals (p = 0.04), particularly in the β-propeller domain (p = 0.04), with 2 rare variants located in the predicted binding site for GRN (p = 0.001). We extended these observations by analyzing 3 independent patient/control cohorts sampled in Spain, Italy, and Portugal by partners of the European Early-Onset Dementia Consortium, together with 1155 FTD patients and 1161 control persons. An additional 7 patient-only nonsynonymous variants were observed in SORT1 in European patients. Meta-analysis of the rare nonsynonymous variants in the Belgian and European patient/control cohorts revealed a significant enrichment in FTD patients (p = 0.006), establishing SORT1 as a genetic risk factor for FTD.
Related Concept Videos
Dementia
The progression of dementia is generally gradual....
Histone Variants at the Centromere
Increasing Function
Relative Risk
Increased Body Temperature
Increased pulse rate
Many factors can elevate the risk of developing tachycardia. These include advanced age, a family history of arrhythmias, and an...

