Publication
Title
Clinical variability and onset age modifiers in an extended Belgian GRN founder family
Author
Institution/Organisation
Belgian Neurology (BELNEU) Consortium
Abstract
We previously reported a granulin (GRN) null mutation, originating from a common founder, in multiple Belgian families with frontotemporal dementia. Here, we used data of a 10-year follow-up study to describe in detail the clinical heterogeneity observed in this extended founder pedigree. We identified 85 patients and 40 unaffected mutation carriers, belonging to 29 branches of the founder pedigree. Most patients (74.4%) were diagnosed with frontotemporal dementia, while others had a clinical diagnosis of unspecified dementia, Alzheimer's dementia or Parkinson's disease. The observed clinical heterogeneity can guide clinical diagnosis, genetic testing, and counseling of mutation carriers. Onset of initial symptomatology is highly variable, ranging from age 45 to 80 years. Analysis of known modifiers, suggested effects of GRN rs5848, microtubule-associated protein tau H1/H2, and chromosome 9 open reading frame 72 G4C2 repeat length on onset age but explained only a minor fraction of the variability. Contrary, the extended GRN founder family is a valuable source for identifying other onset age modifiers based on exome or genome sequences. These modifiers might be interesting targets for developing disease-modifying therapies.
Language
English
Source (journal)
Neurobiology of aging. - Fayetteville, N.Y.
Publication
Fayetteville, N.Y. : 2018
ISSN
0197-4580
Volume/pages
67(2018), p. 84-94
ISI
000432625600010
Pubmed ID
29653316
Full text (Publisher's DOI)
Full text (open access)
UAntwerpen
Faculty/Department
Research group
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identification
Creation 16.04.2018
Last edited 21.08.2021
To cite this reference