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An R 5 L τ mutation in a subject with a progressive supranuclear palsy phenotype
Author(s) -
Poorkaj Parvoneh,
Muma Nancy A.,
Zhukareva Victoria,
Cochran Elizabeth J.,
Shan Kathleen M.,
Hurtig Howard,
Koller William C.,
Bird Thomas D.,
Trojanowski John Q.,
Lee Virginia M.Y.,
Schellenberg Gerard D.
Publication year - 2002
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.10340
Subject(s) - progressive supranuclear palsy , mutation , point mutation , tau protein , gene isoform , phenotype , biology , genetics , gene , medicine , pathology , alzheimer's disease , disease , atrophy
Abstract MAPT , the gene encoding tau, was screened for mutations in 96 progressive supranuclear palsy subjects. A point mutation ( R 5 L ) was identified in a single progressive supranuclear palsy subject that was not in the other progressive supranuclear palsy subjects or in 96 controls. Functionally, this mutation alters the ability of tau to promote microtubule assembly. Analysis of soluble tau from different brain regions indicates that the mutation does not affect the ratio of tau isoforms synthesized. Aggregated insoluble tau from subcortical regions was predominantly four‐repeat tau with no or one amino terminal insert (0N4R and 1N4R). Insoluble tau from cortical regions also contained 1N3R tau. Thus, the R 5 L mutation causes a progressive supranuclear palsy phenotype, presumably by a gain‐of‐function mechanism.