Investigating the role of ALS genes CHCHD10 and TUBA4A in Belgian FTD-ALS spectrum patients

doi:10.1016/j.neurobiolaging.2016.12.008

Case Reports

. 2017 Mar:51:177.e9-177.e16.

doi: 10.1016/j.neurobiolaging.2016.12.008. Epub 2016 Dec 21.

Investigating the role of ALS genes CHCHD10 and TUBA4A in Belgian FTD-ALS spectrum patients

Federica Perrone¹, Hung Phuoc Nguyen¹, Sara Van Mossevelde¹, Matthieu Moisse², Anne Sieben³, Patrick Santens⁴, Jan De Bleecker⁴, Mathieu Vandenbulcke⁵, Sebastiaan Engelborghs⁶, Jonathan Baets⁷, Patrick Cras⁸, Rik Vandenberghe⁹, Peter De Jonghe⁷, Peter P De Deyn⁶, Jean-Jacques Martin¹⁰, Philip Van Damme¹¹, Christine Van Broeckhoven¹², Julie van der Zee¹³; Belgian Neurology consortium

Collaborators, Affiliations

Collaborators

Belgian Neurology consortium:
Dirk Nuytten, Katrien Smets, Jan Versijpt, Alex Michotte, Adrian Ivanoiu, Olivier Deryck, Bruno Bergmans, Jean Delbeck, Marc Bruyland, Christiana Willems, Eric Salmon

Affiliations

¹ Neurodegenerative Brain Diseases Group, Center for Molecular Neurology, VIB, Antwerp, Belgium; Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
² Department of Neurosciences, Faculty of Medicine, KU Leuven, Leuven, Belgium; Laboratory of Neurobiology, Vesalius Research Center, VIB, Leuven, Belgium.
³ Neurodegenerative Brain Diseases Group, Center for Molecular Neurology, VIB, Antwerp, Belgium; Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium; Department of Neurology, University Hospital Ghent and University of Ghent, Ghent, Belgium.
⁴ Department of Neurology, University Hospital Ghent and University of Ghent, Ghent, Belgium.
⁵ Department of Neurosciences, Faculty of Medicine, KU Leuven, Leuven, Belgium; Department of Old Age Psychiatry and Memory Clinic, University of Leuven, Leuven, Belgium.
⁶ Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium; Department of Neurology and Memory Clinic, Hospital Network Antwerp Middelheim and Hoge Beuken, Antwerp, Belgium.
⁷ Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium; Neurogenetics Group, Department of Molecular Genetics, VIB, Antwerp, Belgium; Department of Neurology, Antwerp University Hospital, Antwerp, Belgium.
⁸ Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium; Department of Neurology, Antwerp University Hospital, Antwerp, Belgium.
⁹ Department of Neurosciences, Faculty of Medicine, KU Leuven, Leuven, Belgium; Department of Neurology, University Hospitals Leuven, Leuven, Belgium.
¹⁰ Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
¹¹ Department of Neurosciences, Faculty of Medicine, KU Leuven, Leuven, Belgium; Laboratory of Neurobiology, Vesalius Research Center, VIB, Leuven, Belgium; Department of Neurology, University Hospitals Leuven, Leuven, Belgium.
¹² Neurodegenerative Brain Diseases Group, Center for Molecular Neurology, VIB, Antwerp, Belgium; Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium. Electronic address: christine.vanbroeckhoven@molgen.vib-ua.be.
¹³ Neurodegenerative Brain Diseases Group, Center for Molecular Neurology, VIB, Antwerp, Belgium; Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium. Electronic address: julie.vanderzee@molgen.vib-ua.be.

PMID: 28069311
DOI: 10.1016/j.neurobiolaging.2016.12.008

Free article

Case Reports

Investigating the role of ALS genes CHCHD10 and TUBA4A in Belgian FTD-ALS spectrum patients

Federica Perrone et al. Neurobiol Aging. 2017 Mar.

Free article

. 2017 Mar:51:177.e9-177.e16.

doi: 10.1016/j.neurobiolaging.2016.12.008. Epub 2016 Dec 21.

Authors

Collaborators

Belgian Neurology consortium:
Dirk Nuytten, Katrien Smets, Jan Versijpt, Alex Michotte, Adrian Ivanoiu, Olivier Deryck, Bruno Bergmans, Jean Delbeck, Marc Bruyland, Christiana Willems, Eric Salmon

Affiliations

¹ Neurodegenerative Brain Diseases Group, Center for Molecular Neurology, VIB, Antwerp, Belgium; Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
² Department of Neurosciences, Faculty of Medicine, KU Leuven, Leuven, Belgium; Laboratory of Neurobiology, Vesalius Research Center, VIB, Leuven, Belgium.
³ Neurodegenerative Brain Diseases Group, Center for Molecular Neurology, VIB, Antwerp, Belgium; Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium; Department of Neurology, University Hospital Ghent and University of Ghent, Ghent, Belgium.
⁴ Department of Neurology, University Hospital Ghent and University of Ghent, Ghent, Belgium.
⁵ Department of Neurosciences, Faculty of Medicine, KU Leuven, Leuven, Belgium; Department of Old Age Psychiatry and Memory Clinic, University of Leuven, Leuven, Belgium.
⁶ Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium; Department of Neurology and Memory Clinic, Hospital Network Antwerp Middelheim and Hoge Beuken, Antwerp, Belgium.
⁷ Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium; Neurogenetics Group, Department of Molecular Genetics, VIB, Antwerp, Belgium; Department of Neurology, Antwerp University Hospital, Antwerp, Belgium.
⁸ Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium; Department of Neurology, Antwerp University Hospital, Antwerp, Belgium.
⁹ Department of Neurosciences, Faculty of Medicine, KU Leuven, Leuven, Belgium; Department of Neurology, University Hospitals Leuven, Leuven, Belgium.
¹⁰ Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
¹¹ Department of Neurosciences, Faculty of Medicine, KU Leuven, Leuven, Belgium; Laboratory of Neurobiology, Vesalius Research Center, VIB, Leuven, Belgium; Department of Neurology, University Hospitals Leuven, Leuven, Belgium.
¹² Neurodegenerative Brain Diseases Group, Center for Molecular Neurology, VIB, Antwerp, Belgium; Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium. Electronic address: christine.vanbroeckhoven@molgen.vib-ua.be.
¹³ Neurodegenerative Brain Diseases Group, Center for Molecular Neurology, VIB, Antwerp, Belgium; Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium. Electronic address: julie.vanderzee@molgen.vib-ua.be.

PMID: 28069311
DOI: 10.1016/j.neurobiolaging.2016.12.008

Abstract

Mutation screening and phenotypic profiling of 2 amyotrophic lateral sclerosis-(ALS) and frontotemporal dementia-(FTD) associated genes, CHCHD10 and TUBA4A, were performed in a Belgian cohort of 459 FTD, 28 FTD-ALS, and 429 ALS patients. In CHCHD10, we identified a novel nonsense mutation (p.Gln108*) in a patient with atypical clinical FTD and pathology-confirmed Parkinson's disease (1/459, 0.22%) leading to loss of transcript. We further observed 3 previously described missense variants (p.Pro34Ser, p.Pro80Leu, and p.Pro96Thr) that were also present in the matched control series. In TUBA4A, we detected a novel frameshift mutation (p.Arg64Glyfs*90) leading to a truncated protein in 1 FTD patient (1/459 of 0.22%) with family history of Parkinson's disease and cognitive impairment, and a novel missense mutation (p.Thr381Met) in 2 sibs with familial ALS and memory problems (1 index patient/429, 0.23%) in whom we previously identified a pathogenic Chromosome 9 open reading frame 72 repeat expansion mutation. The present study confirms the role of CHCHD10 and TUBA4A in the FTD-ALS spectrum, although genetic variations in these 2 genes are extremely rare in the Belgian population and often associated with symptomatology of related neurodegenerative diseases including Parkinson's disease and Alzheimer's disease.

Keywords: Amyotrophic lateral sclerosis (ALS); CHCHD10; Frontotemporal dementia (FTD); TUBA4A.

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Investigating the role of ALS genes CHCHD10 and TUBA4A in Belgian FTD-ALS spectrum patients

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Investigating the role of ALS genes CHCHD10 and TUBA4A in Belgian FTD-ALS spectrum patients

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