Mutations in progranulin explain atypical phenotypes with variants in MAPT.
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.
Pickering-Brown
Stuart M
SM
Baker
Matt
M
Gass
Jenny
J
Boeve
Bradley F
BF
Loy
Clement T
CT
Brooks
William S
WS
Mackenzie
Ian R A
IR
Martins
Ralph N
RN
Kwok
John B J
JB
Halliday
Glenda M
GM
Kril
Jillian
J
Schofield
Peter R
PR
Mann
David M A
DM
Hutton
Mike
M
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*
C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; C054369:MAPT protein, human; D000077153:Progranulins; D025801:Ubiquitin; D016875:tau Proteins