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.

DESIGN

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.