TDP-43 is not a common cause of sporadic amyotrophic lateral sclerosis.
BACKGROUND
TAR DNA binding protein, encoded by TARDBP, was shown to be a central component of ubiquitin-positive, tau-negative inclusions in frontotemporal lobar degeneration (FTLD-U) and amyotrophic lateral sclerosis (ALS). Recently, mutations in TARDBP have been linked to familial and sporadic ALS.


RESULTS
To further examine the frequency of mutations in TARDBP in sporadic ALS, 279 ALS cases and 806 neurologically normal control individuals of European descent were screened for sequence variants, copy number variants, genetic and haplotype association with disease. An additional 173 African samples from the Human Gene Diversity Panel were sequenced as this population had the highest likelihood of finding changes. No mutations were found in the ALS cases. Several genetic variants were identified in controls, which were considered as non-pathogenic changes. Furthermore, pathogenic structural variants were not observed in the cases and there was no genetic or haplotype association with disease status across the TARDBP locus.


CONCLUSIONS
Our data indicate that genetic variation in TARDBP is not a common cause of sporadic ALS in North American.
Laboratory of Neurogenetics, National Institute of Aging, National Institutes of Health, Bethesda, Maryland, United States of America. portalegrer@nia.nih.gov
Rita J
RJ
Guerreiro
Jennifer C
JC
Schymick
Cynthia
C
Crews
Andrew
A
Singleton
John
J
Hardy
Bryan J
BJ
Traynor
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000503:physiopathology*; D015331:Cohort Studies; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D016013:Likelihood Functions; D008875:Middle Aged; D009154:Mutation; D020641:Polymorphism, Single Nucleotide
D004268:DNA-Binding Proteins