title: Investigating the role of ALS genes CHCHD10 and TUBA4A in Belgian FTD-ALS spectrum patients.
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.
authors.affiliation: Neurodegenerative Brain Diseases Group, Center for Molecular Neurology, VIB, Antwerp, Belgium; Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
authors.forename: Federica
authors.initials: F
authors.lastname: Perrone
authors.affiliation: Neurodegenerative Brain Diseases Group, Center for Molecular Neurology, VIB, Antwerp, Belgium; Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
authors.forename: Hung Phuoc
authors.initials: HP
authors.lastname: Nguyen
authors.affiliation: Neurodegenerative Brain Diseases Group, Center for Molecular Neurology, VIB, Antwerp, Belgium; Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
authors.forename: Sara
authors.initials: S
authors.lastname: Van Mossevelde
authors.affiliation: Department of Neurosciences, Faculty of Medicine, KU Leuven, Leuven, Belgium; Laboratory of Neurobiology, Vesalius Research Center, VIB, Leuven, Belgium.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Moisse
authors.affiliation: 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.
authors.forename: Anne
authors.initials: A
authors.lastname: Sieben
authors.affiliation: Department of Neurology, University Hospital Ghent and University of Ghent, Ghent, Belgium.
authors.forename: Patrick
authors.initials: P
authors.lastname: Santens
authors.affiliation: Department of Neurology, University Hospital Ghent and University of Ghent, Ghent, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: De Bleecker
authors.affiliation: Department of Neurosciences, Faculty of Medicine, KU Leuven, Leuven, Belgium; Department of Old Age Psychiatry and Memory Clinic, University of Leuven, Leuven, Belgium.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Vandenbulcke
authors.affiliation: 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.
authors.forename: Sebastiaan
authors.initials: S
authors.lastname: Engelborghs
authors.affiliation: 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.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Baets
authors.affiliation: Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium; Department of Neurology, Antwerp University Hospital, Antwerp, Belgium.
authors.forename: Patrick
authors.initials: P
authors.lastname: Cras
authors.affiliation: Department of Neurosciences, Faculty of Medicine, KU Leuven, Leuven, Belgium; Department of Neurology, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Rik
authors.initials: R
authors.lastname: Vandenberghe
authors.affiliation: 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.
authors.forename: Peter
authors.initials: P
authors.lastname: De Jonghe
authors.affiliation: 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.
authors.forename: Peter P
authors.initials: PP
authors.lastname: De Deyn
authors.affiliation: Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Martin
authors.affiliation: 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.
authors.forename: Philip
authors.initials: P
authors.lastname: Van Damme
authors.affiliation: 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.
authors.forename: Christine
authors.initials: C
authors.lastname: Van Broeckhoven
authors.affiliation: 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.
authors.forename: Julie
authors.initials: J
authors.lastname: van der Zee
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D001530:Belgium; D015331:Cohort Studies; D005260:Female; D057180:Frontotemporal Dementia / Q000235:genetics*; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics*; D009154:Mutation; D014404:Tubulin / Q000235:genetics*
chemical_list: C554426:CHCHD10 protein, human; D024101:Mitochondrial Proteins; D014404:Tubulin
keywords: Amyotrophic lateral sclerosis (ALS); CHCHD10; Frontotemporal dementia (FTD); TUBA4A