title: A new mutation of the tau gene, G303V, in early-onset familial progressive supranuclear palsy.
abstract: 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.
authors.affiliation: Banco de Tejidos para Investigaciones Neurológicas, Universidad Autónoma de Madrid, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Ros
authors.forename: Stéphane
authors.initials: S
authors.lastname: Thobois
authors.forename: Nathalie
authors.initials: N
authors.lastname: Streichenberger
authors.forename: Nicolas
authors.initials: N
authors.lastname: Kopp
authors.forename: Marina P
authors.initials: MP
authors.lastname: Sánchez
authors.forename: Mar
authors.initials: M
authors.lastname: Pérez
authors.forename: Janet
authors.initials: J
authors.lastname: Hoenicka
authors.forename: Jesús
authors.initials: J
authors.lastname: Avila
authors.forename: Jerome
authors.initials: J
authors.lastname: Honnorat
authors.forename: Justo G
authors.initials: JG
authors.lastname: de Yébenes
mesh_terms: 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*
chemical_list: D020033:Protein Isoforms; D012333:RNA, Messenger; D016875:tau Proteins; C043437:fluorodopa F 18; D020891:Raclopride; D004295:Dihydroxyphenylalanine; D014633:Valine; D005998:Glycine