title: [A Pair of Siblings with Frontotemporal Dementia and Amyotrophic Lateral Sclerosis and a Novel Thr462Lysfs Mutation in the TBK1 Gene].
abstract: We report on a pair of siblings with frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) and a novel Thr462Lysfs mutation in the TANK-binding kinase 1 (TBK1) gene identified through the European Early-Onset Dementia Consortium. The patients presented at the age of 77 and 75 years and displayed dementia and bulbar symptoms as well as progressive paresis. After a progressive course, both of them died only a few months after diagnosis. Most recently, TBK1 mutations were identified in patients with FTD and ALS. A loss of expression of the mutant allele, leading to 50 % reduced TBK1 protein levels, seems to be causative. The occurrence of TBK1 mutations in FTD and ALS underlines the fact that FTD and ALS are part of the same disease spectrum. For future therapeutic trials, characterization of TBK1 mutation carriers in presymptomatic cohorts, such as the genetic frontotemporal dementia initiative (GENFI), is of great importance.
authors: Neurologische Klinik und Poliklinik, Ludwig-Maximilians-Universität, München.
authors: S
authors: S
authors: Schönecker
authors: Klinik und Poliklinik für Nuklearmedizin, Ludwig-Maximilians-Universität, München.
authors: M
authors: M
authors: Brendel
authors: Institut Born-Bunge, Universität Antwerpen.
authors: J
authors: J
authors: van der Zee
authors: Institut Born-Bunge, Universität Antwerpen.
authors: C
authors: C
authors: van Broeckhoven
authors: Klinik und Poliklinik für Nuklearmedizin, Ludwig-Maximilians-Universität, München.
authors: A
authors: A
authors: Rominger
authors: Neurologische Klinik und Poliklinik, Ludwig-Maximilians-Universität, München.
authors: A
authors: A
authors: Danek
authors: Neurologische Klinik und Poliklinik, Ludwig-Maximilians-Universität, München.
authors: J
authors: J
authors: Levin
mesh_terms: D000368:Aged; D000483:Alleles; D000690:Amyotrophic Lateral Sclerosis / Q000175:diagnosis / Q000235:genetics*; D001921:Brain / Q000473:pathology; D015897:Comorbidity; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D057180:Frontotemporal Dementia / Q000175:diagnosis / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009460:Neurologic Examination; D010375:Pedigree; D049268:Positron-Emission Tomography; D035781:Siblings