Mutational analysis of TARDBP in neurodegenerative diseases.
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.
Ticozzi
Nicola
N
Department of Neurology, University of Massachusetts Medical School, Worcester, MA 01605, USA. n.ticozzi@fastwebnet.it
LeClerc
Ashley Lyn
AL
van Blitterswijk
Marka
M
Keagle
Pamela
P
McKenna-Yasek
Diane M
DM
Sapp
Peter C
PC
Silani
Vincenzo
V
Wills
Anne-Marie
AM
Brown
Robert H
RH
Landers
John E
JE
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*
D004268:DNA-Binding Proteins