TARDBP mutations in Parkinson's disease

Abstract

Mutations of the TARDBP gene encoding TDP-43 protein have been shown to cause amyotrophic lateral sclerosis and have been reported to present with clinical heterogeneity including parkinsonism. In addition, TDP-43 pathology has been observed across a spectrum of neurodegenerative disorders, including Alzheimer's and Parkinson's disease. Herein we report the presence of a TDP-43 mutation in a patient with a clinical diagnosis of Parkinson's disease. The TDP-43 p.N267S substitution has been previously implicated in both amyotrophic lateral sclerosis and behavioral variant frontotemporal dementia. Our findings widen the phenotypic presentation for the TDP-43 p.N267S substitution and support a possible role for rare TDP-43 mutations presenting with Parkinson's disease.

Figure 1. Pedigree of the TDP-43 p.N267S proband

Arrow indicates proband. Squares represent males, circles represent females. Darkened symbols indicate affected individuals (phenotypes in the right upper corner). A diagonal line through a symbol means deceased. Number indicates number of offspring. To protect patient confidentiality, the birth order was modified, gender was masked in some individuals and mutation status is not highlighted. Subjects with clinical phenotype accompanied by mild behavioral problems^$, or accompanied by severe behavioral problems^# are noted.