A novel presenilin 1 mutation associated with Pick's disease but not β-amyloid plaques
Bart Dermaut MD, PhD
Department of Molecular Genetics, Flanders Interuniversity Institute of Biotechnology (VIB8), University of Antwerp, Antwerpen, Belgium
Search for more papers by this authorSamir Kumar-Singh MD, PhD
Department of Molecular Genetics, Flanders Interuniversity Institute of Biotechnology (VIB8), University of Antwerp, Antwerpen, Belgium
Search for more papers by this authorSebastian Engelborghs MD
Laboratory of Neurochemistry and Behavior, Department of Biomedical Sciences, Born-Bunge Foundation, University of Antwerp, Antwerpen, Belgium
Department of Neurology and Memory Clinic, Middelheim General Hospital, Antwerpen, Belgium
Search for more papers by this authorJessie Theuns PhD
Department of Molecular Genetics, Flanders Interuniversity Institute of Biotechnology (VIB8), University of Antwerp, Antwerpen, Belgium
Search for more papers by this authorRosa Rademakers MSc
Department of Molecular Genetics, Flanders Interuniversity Institute of Biotechnology (VIB8), University of Antwerp, Antwerpen, Belgium
Search for more papers by this authorJos Saerens MSc
Department of Neurology and Memory Clinic, Middelheim General Hospital, Antwerpen, Belgium
Search for more papers by this authorBarbara A. Pickut MD
Department of Neurology and Memory Clinic, Middelheim General Hospital, Antwerpen, Belgium
Search for more papers by this authorKarin Peeters
Department of Molecular Genetics, Flanders Interuniversity Institute of Biotechnology (VIB8), University of Antwerp, Antwerpen, Belgium
Search for more papers by this authorMarleen Van Den Broeck
Department of Molecular Genetics, Flanders Interuniversity Institute of Biotechnology (VIB8), University of Antwerp, Antwerpen, Belgium
Search for more papers by this authorKrist'l Vennekens
Department of Molecular Genetics, Flanders Interuniversity Institute of Biotechnology (VIB8), University of Antwerp, Antwerpen, Belgium
Search for more papers by this authorStephen Claes MD, PhD
Department of Molecular Genetics, Flanders Interuniversity Institute of Biotechnology (VIB8), University of Antwerp, Antwerpen, Belgium
Search for more papers by this authorMarc Cruts PhD
Department of Molecular Genetics, Flanders Interuniversity Institute of Biotechnology (VIB8), University of Antwerp, Antwerpen, Belgium
Search for more papers by this authorPatrick Cras MD, PhD
Laboratory of Neurobiology, Born Bunge Foundation, University of Antwerp, Antwerpen, Belgium
Search for more papers by this authorJean-Jacques Martin MD, PhD
Laboratory of Neuropathology, Born Bunge Foundation, University of Antwerp, Antwerpen, Belgium
Search for more papers by this authorCorresponding Author
Christine Van Broeckhoven PhD, DSc
Department of Molecular Genetics, Flanders Interuniversity Institute of Biotechnology (VIB8), University of Antwerp, Antwerpen, Belgium
Department of Molecular Genetics (VIB8), University of Antwerp, Universiteitsplein 1, B-2610, Antwerpen, BelgiumSearch for more papers by this authorPeter Paul De Deyn MD, PhD
Laboratory of Neurochemistry and Behavior, Department of Biomedical Sciences, Born-Bunge Foundation, University of Antwerp, Antwerpen, Belgium
Department of Neurology and Memory Clinic, Middelheim General Hospital, Antwerpen, Belgium
Search for more papers by this authorBart Dermaut MD, PhD
Department of Molecular Genetics, Flanders Interuniversity Institute of Biotechnology (VIB8), University of Antwerp, Antwerpen, Belgium
Search for more papers by this authorSamir Kumar-Singh MD, PhD
Department of Molecular Genetics, Flanders Interuniversity Institute of Biotechnology (VIB8), University of Antwerp, Antwerpen, Belgium
Search for more papers by this authorSebastian Engelborghs MD
Laboratory of Neurochemistry and Behavior, Department of Biomedical Sciences, Born-Bunge Foundation, University of Antwerp, Antwerpen, Belgium
Department of Neurology and Memory Clinic, Middelheim General Hospital, Antwerpen, Belgium
Search for more papers by this authorJessie Theuns PhD
Department of Molecular Genetics, Flanders Interuniversity Institute of Biotechnology (VIB8), University of Antwerp, Antwerpen, Belgium
Search for more papers by this authorRosa Rademakers MSc
Department of Molecular Genetics, Flanders Interuniversity Institute of Biotechnology (VIB8), University of Antwerp, Antwerpen, Belgium
Search for more papers by this authorJos Saerens MSc
Department of Neurology and Memory Clinic, Middelheim General Hospital, Antwerpen, Belgium
Search for more papers by this authorBarbara A. Pickut MD
Department of Neurology and Memory Clinic, Middelheim General Hospital, Antwerpen, Belgium
Search for more papers by this authorKarin Peeters
Department of Molecular Genetics, Flanders Interuniversity Institute of Biotechnology (VIB8), University of Antwerp, Antwerpen, Belgium
Search for more papers by this authorMarleen Van Den Broeck
Department of Molecular Genetics, Flanders Interuniversity Institute of Biotechnology (VIB8), University of Antwerp, Antwerpen, Belgium
Search for more papers by this authorKrist'l Vennekens
Department of Molecular Genetics, Flanders Interuniversity Institute of Biotechnology (VIB8), University of Antwerp, Antwerpen, Belgium
Search for more papers by this authorStephen Claes MD, PhD
Department of Molecular Genetics, Flanders Interuniversity Institute of Biotechnology (VIB8), University of Antwerp, Antwerpen, Belgium
Search for more papers by this authorMarc Cruts PhD
Department of Molecular Genetics, Flanders Interuniversity Institute of Biotechnology (VIB8), University of Antwerp, Antwerpen, Belgium
Search for more papers by this authorPatrick Cras MD, PhD
Laboratory of Neurobiology, Born Bunge Foundation, University of Antwerp, Antwerpen, Belgium
Search for more papers by this authorJean-Jacques Martin MD, PhD
Laboratory of Neuropathology, Born Bunge Foundation, University of Antwerp, Antwerpen, Belgium
Search for more papers by this authorCorresponding Author
Christine Van Broeckhoven PhD, DSc
Department of Molecular Genetics, Flanders Interuniversity Institute of Biotechnology (VIB8), University of Antwerp, Antwerpen, Belgium
Department of Molecular Genetics (VIB8), University of Antwerp, Universiteitsplein 1, B-2610, Antwerpen, BelgiumSearch for more papers by this authorPeter Paul De Deyn MD, PhD
Laboratory of Neurochemistry and Behavior, Department of Biomedical Sciences, Born-Bunge Foundation, University of Antwerp, Antwerpen, Belgium
Department of Neurology and Memory Clinic, Middelheim General Hospital, Antwerpen, Belgium
Search for more papers by this authorAbstract
Familial forms of frontotemporal dementia (FTD) with tauopathy are mostly caused by mutations in the gene encoding the microtubule-associated protein tau (MAPT). However, rare forms of familial tauopathy without MAPT mutations have been reported, suggesting other tauopathy-related genetic defects. Interestingly, two presenilin 1 (PS1) mutations (Leu113Pro and insArg352) recently have been associated with familial FTD albeit without neuropathological confirmation. We report here a novel PS1 mutation in a patient with Pick-type tauopathy in the absence of extracellular β-amyloid deposits. The mutation is predicted to substitute Gly→Val at codon position 183 (Gly183Val) and to affect the splice signal at the junction of the sixth exon and intron. Further clinical-genetic investigation showed a positive family history of FTD-like dementia and suggested that Gly183Val is associated with a phenotypically heterogeneous neurodegenerative disorder. Our results suggest PS1 as a candidate gene for Pick-type tauopathy without MAPT mutations.
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