Frontotemporal dementia and corticobasal degeneration in a family with a P301S mutation in tau.
The tau gene has been found to be the locus of dementia with rigidity linked to chromosome 17. Exonic and intronic mutations have been described in a number of families. Here we describe a P301S mutation in exon 10 of the tau gene in a new family. Two members of this family were affected. One individual presented with frontotemporal dementia, whereas his son has corticobasal degeneration, demonstrating that the same primary gene defect in tau can lead to 2 distinct clinical phenotypes. Both individuals developed rapidly progressive disease in the third decade. Neuropathologically, the father presented with an extensive filamentous pathology made of hyperphosphorylated tau protein. Biochemically, recombinant tau protein with the P301S mutation showed a greatly reduced ability to promote microtubule assembly.
Bugiani
O
O
Istituto Neurologico Carlo Besta, Milano, Italy.
Murrell
J R
JR
Giaccone
G
G
Hasegawa
M
M
Ghigo
G
G
Tabaton
M
M
Morbin
M
M
Primavera
A
A
Carella
F
F
Solaro
C
C
Grisoli
M
M
Savoiardo
M
M
Spillantini
M G
MG
Tagliavini
F
F
Goedert
M
M
Ghetti
B
B
D000328:Adult; D001480:Basal Ganglia Diseases / Q000473:pathology*; D002540:Cerebral Cortex / Q000473:pathology*; D004247:DNA / Q000235:genetics; D003704:Dementia / Q000235:genetics* / Q000473:pathology; D005192:Family Health; D005625:Frontal Lobe / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008870:Microtubules / Q000648:ultrastructure; D008875:Middle Aged; D009154:Mutation; D009410:Nerve Degeneration; D010375:Pedigree; D013702:Temporal Lobe / Q000473:pathology*; D016875:tau Proteins / Q000235:genetics
D016875:tau Proteins; D004247:DNA