A new mutation of the tau gene, G303V, in early-onset familial progressive supranuclear palsy.
BACKGROUND
Progressive supranuclear palsy (PSP) is a clinicopathological syndrome related to tau deposits and in linkage disequilibrium with tau polymorphisms. Some rare familial PSP cases have been related to tau gene mutations.


OBJECTIVE
To present the clinical, pathological, and molecular data of one family with early-onset autosomal dominant PSP.


METHODS
We performed clinical examinations, quantitative neurological tests, positron emission tomographic scans with fluorodopa F 18 and raclopride C 11, analysis of tau mutations, neuropathological examinations, and protein analyses on brain specimens.


RESULTS
Three family members had PSP confirmed by pathological features in the proband. A novel mutation of tau, G303V, was found in the proband and other family members. tau Isoforms with 4 microtubule-binding repeats were overexpressed in the proband brain.


CONCLUSIONS
The G303V mutation of tau is associated with autosomal dominant PSP. Expression of 4 microtubule-binding repeat tau isoforms is increased in the proband.
Ros
Raquel
R
Banco de Tejidos para Investigaciones Neurológicas, Universidad Autónoma de Madrid, Spain.
Thobois
Stéphane
S
Streichenberger
Nathalie
N
Kopp
Nicolas
N
Sánchez
Marina P
MP
Pérez
Mar
M
Hoenicka
Janet
J
Avila
Jesús
J
Honnorat
Jerome
J
de Yébenes
Justo G
JG
D019943:Amino Acid Substitution; D015152:Blotting, Northern; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000378:metabolism; D004252:DNA Mutational Analysis / Q000379:methods; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives / Q000378:metabolism; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease; D005998:Glycine / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008875:Middle Aged; D009154:Mutation; D009460:Neurologic Examination; D049268:Positron-Emission Tomography / Q000379:methods; D020033:Protein Isoforms / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D020891:Raclopride / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013494:Supranuclear Palsy, Progressive / Q000235:genetics* / Q000473:pathology; D014633:Valine / Q000235:genetics*; D016875:tau Proteins / Q000235:genetics*
D020033:Protein Isoforms; D012333:RNA, Messenger; D016875:tau Proteins; C043437:fluorodopa F 18; D020891:Raclopride; D004295:Dihydroxyphenylalanine; D014633:Valine; D005998:Glycine