TARDBP variation associated with frontotemporal dementia, supranuclear gaze palsy, and chorea.
TDP-43 has been identified as the pathological protein in the majority of cases of frontotemporal lobar degeneration and amyotrophic lateral sclerosis (ALS). TARDBP mutations have so far been uniquely associated with familial and sporadic ALS. We describe clinicopathological and genetic findings in a carrier of the novel K263E TARDBP variation, who developed frontotemporal dementia, supranuclear palsy, and chorea, but no signs of motor neuron disease. Neuropathologic examination revealed neuronal and glial TDP-43-immunoreactive deposits, predominantly in subcortical nuclei and brainstem. This is the first report of a TARDBP variation associated with a neurodegenerative syndrome other than ALS.
Kovacs
Gabor G
GG
Institute of Neurology, Medical University of Vienna, Vienna, Austria.
Murrell
Jill R
JR
Horvath
Sandor
S
Haraszti
Laszlo
L
Majtenyi
Katalin
K
Molnar
Maria J
MJ
Budka
Herbert
H
Ghetti
Bernardino
B
Spina
Salvatore
S
D002819:Chorea / Q000175:diagnosis / Q000235:genetics*; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005192:Family Health; D005260:Female; D057180:Frontotemporal Dementia / Q000175:diagnosis / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D018698:Glutamic Acid / Q000235:genetics; D006801:Humans; D008239:Lysine / Q000235:genetics; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009483:Neuropsychological Tests; D013494:Supranuclear Palsy, Progressive / Q000175:diagnosis / Q000235:genetics*; D015898:Tomography Scanners, X-Ray Computed
D004268:DNA-Binding Proteins; D018698:Glutamic Acid; D008239:Lysine