title: Mutational analysis of TARDBP in neurodegenerative diseases.
abstract: Neurodegenerative diseases are often characterized by the presence of aggregates of misfolded proteins. TDP-43 is a major component of these aggregates in amyotrophic lateral sclerosis (ALS), but has also been observed in Alzheimer's (AD) and Parkinson's Diseases (PD). In addition, mutations in the TARDBP gene, encoding TDP-43, have been found to be a significant cause of familial ALS (FALS). All mutations, except for one, have been found in exon 6. To confirm this observation in ALS and to investigate whether TARDBP may play a role in the pathogenesis of AD and PD, we screened for mutations in exon 6 of the TARDBP gene in three cohorts composed of 376 AD, 463 PD (18% familial PD) and 376 ALS patients (50% FALS). We found mutations in ∼ 7% of FALS and ∼0.5% of sporadic ALS (SALS) patients, including two novel mutations, p.N352T and p.G384R. In contrast, we did not find TARDBP mutations in our cohort of AD and PD patients. These results suggest that mutations in TARDBP are not a significant cause of AD and PD.
authors.affiliation: Department of Neurology, University of Massachusetts Medical School, Worcester, MA 01605, USA. n.ticozzi@fastwebnet.it
authors.forename: Nicola
authors.initials: N
authors.lastname: Ticozzi
authors.forename: Ashley Lyn
authors.initials: AL
authors.lastname: LeClerc
authors.forename: Marka
authors.initials: M
authors.lastname: van Blitterswijk
authors.forename: Pamela
authors.initials: P
authors.lastname: Keagle
authors.forename: Diane M
authors.initials: DM
authors.lastname: McKenna-Yasek
authors.forename: Peter C
authors.initials: PC
authors.lastname: Sapp
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Silani
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Wills
authors.forename: Robert H
authors.initials: RH
authors.lastname: Brown
authors.forename: John E
authors.initials: JE
authors.lastname: Landers
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics*; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D005091:Exons; D006801:Humans; D009154:Mutation; D010300:Parkinson Disease / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins