Rare non-synonymous variants in SORT1 are associated with increased risk for frontotemporal dementia

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 1,066 unaffected control individuals, we identified five patient-only non-synonymous 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 two rare variants located in the predicted binding site for GRN (p=0.001).

Source: Neurobiology of Aging - February 17, 2018 Category: Neuroscience Authors: St éphanie Philtjens, Sara Van Mossevelde, Julie van der Zee, Eline Wauters, Lubina Dillen, Mathieu Vandenbulcke, Rik Vandenberghe, Adrian Ivanoiu, Anne Sieben, Christiana Willems, Luisa Benussi, Roberta Ghidoni, Giuliano Binetti, Barbara Borroni, Alessa Source Type: research