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Title: | Clinical variability and onset age modifiers in an extended Belgian GRN founder family | Authors: | Wauters, Eline Van Mossevelde, Sara Sleegers, Kristel van der Zee, Julie Engelborghs, Sebastiaan Sieben, Anne Vandenberghe, Rik PHILTJENS, Stephanie Van den Broeck, Marleen Peeters, Karin Cuijt, Ivy De Coster, Wouter Van Langenhove, Tim Santens, Patrick Ivanoiu, Adrian Cras, Patrick De Bleecker, Jan L. Versijpt, Jan Crols, Roeland DE KLIPPEL, Nina Martin, Jean-Jacques De Deyn, Peter P. Cruts, Marc Van Broeckhoven, Christine |
Issue Date: | 2018 | Publisher: | ELSEVIER SCIENCE INC | Source: | NEUROBIOLOGY OF AGING, 67, p. 84-94 | 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 H-1/H-2, and chromosome 9 open reading frame 72 G(4)C(2) 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. (C) 2018 The Authors. Published by Elsevier Inc. | Notes: | [Wauters, Eline; Van Mossevelde, Sara; Sleegers, Kristel; van der Zee, Julie; Sieben, Anne; Philtjens, Stephanie; Van den Broeck, Marleen; Peeters, Karin; Cuijt, Ivy; De Coster, Wouter; De Deyn, Peter P.; Cruts, Marc; Van Broeckhoven, Christine] VIB, Ctr Mol Neurol, Antwerp, Belgium. [Wauters, Eline; Van Mossevelde, Sara; Sleegers, Kristel; van der Zee, Julie; Engelborghs, Sebastiaan; Sieben, Anne; Philtjens, Stephanie; Van den Broeck, Marleen; Peeters, Karin; Cuijt, Ivy; De Coster, Wouter; Cras, Patrick; Martin, Jean-Jacques; De Deyn, Peter P.; Cruts, Marc] Inst Born Bunge, Antwerp, Belgium. [Wauters, Eline; Van Mossevelde, Sara; Sleegers, Kristel; van der Zee, Julie; Engelborghs, Sebastiaan; Sieben, Anne; Philtjens, Stephanie; Van den Broeck, Marleen; Peeters, Karin; Cuijt, Ivy; De Coster, Wouter; Cras, Patrick; Martin, Jean-Jacques; De Deyn, Peter P.; Cruts, Marc] Univ Antwerp, Antwerp, Belgium. [Van Mossevelde, Sara; Cras, Patrick] Antwerp Univ Hosp, Dept Neurol, Edegem, Belgium. [Engelborghs, Sebastiaan; Crols, Roeland; De Deyn, Peter P.] Hosp Network Antwerp Middelheim & Hoge Beuken, Dept Neurol, Antwerp, Belgium. [Engelborghs, Sebastiaan; Crols, Roeland; De Deyn, Peter P.] Hosp Network Antwerp Middelheim & Hoge Beuken, Memory Clin, Antwerp, Belgium. [Sieben, Anne; Van Langenhove, Tim; Santens, Patrick; De Bleecker, Jan L.] Univ Ghent, Dept Neurol, Ghent, Belgium. [Sieben, Anne; Van Langenhove, Tim; Santens, Patrick; De Bleecker, Jan L.] Univ Hosp Ghent, Ghent, Belgium. [Vandenberghe, Rik] Katholieke Univ Leuven, Fac Med, Dept Neurosci, Leuven, Belgium. [Vandenberghe, Rik] Univ Hosp Leuven, Dept Neurol, Leuven, Belgium. [Ivanoiu, Adrian] St Luc Univ Hosp, Dept Neurol, Brussels, Belgium. [Ivanoiu, Adrian] Catholic Univ Louvain, Inst Neurosci, Brussels, Belgium. [Versijpt, Jan] Univ Brussels VUB, Univ Hosp Brussel UZ Brussel, Dept Neurol, Brussels, Belgium. [De Klippel, Nina] Jessa Hosp, Neurol Serv, Hasselt, Belgium. | Keywords: | Frontotemporal dementia; Clinical heterogeneity; GRN; Founder pedigree; Modifiers;Frontotemporal dementia; Clinical heterogeneity; GRN; Founder pedigree; Modifiers | Document URI: | http://hdl.handle.net/1942/28607 | ISSN: | 0197-4580 | e-ISSN: | 1558-1497 | DOI: | 10.1016/j.neurobiolaging.2018.03.007 | ISI #: | 000432625600010 | Rights: | Copyright 2018 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). | Category: | A1 | Type: | Journal Contribution |
Appears in Collections: | Research publications |
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