title: Mutations in progranulin explain atypical phenotypes with variants in MAPT.
abstract: Mutations in presenilin-1 (PSEN1) cause autosomal dominant Alzheimer's disease and mutations in MAPT cause the familial tauopathy Frontotemporal dementia linked to chromosome 17 (FTDP-17). However, there have been reports of mutations in PSEN1 and MAPT associated with cases of FTD with ubiquitin-positive tau-negative inclusion pathology. Here, we demonstrate that the MAPT variants are almost certainly rare benign polymorphisms as all of these cases harbour mutations in Progranulin (PGRN). Mutations in PGRN were recently shown to cause ubiquitin-positive FTDP-17.
authors.forename: Stuart M
authors.initials: SM
authors.lastname: Pickering-Brown
authors.forename: Matt
authors.initials: M
authors.lastname: Baker
authors.forename: Jenny
authors.initials: J
authors.lastname: Gass
authors.forename: Bradley F
authors.initials: BF
authors.lastname: Boeve
authors.forename: Clement T
authors.initials: CT
authors.lastname: Loy
authors.forename: William S
authors.initials: WS
authors.lastname: Brooks
authors.forename: Ian R A
authors.initials: IR
authors.lastname: Mackenzie
authors.forename: Ralph N
authors.initials: RN
authors.lastname: Martins
authors.forename: John B J
authors.initials: JB
authors.lastname: Kwok
authors.forename: Glenda M
authors.initials: GM
authors.lastname: Halliday
authors.forename: Jillian
authors.initials: J
authors.lastname: Kril
authors.forename: Peter R
authors.initials: PR
authors.lastname: Schofield
authors.forename: David M A
authors.initials: DM
authors.lastname: Mann
authors.forename: Mike
authors.initials: M
authors.lastname: Hutton
mesh_terms: D001483:Base Sequence; D003704:Dementia / Q000235:genetics*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D000077153:Progranulins; D025801:Ubiquitin / Q000378:metabolism; D016875:tau Proteins / Q000235:genetics*
chemical_list: C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; C054369:MAPT protein, human; D000077153:Progranulins; D025801:Ubiquitin; D016875:tau Proteins