title: Novel progranulin mutation: screening for PGRN mutations in a Portuguese series of FTD/CBS cases.
abstract: Mutations in the progranulin (PGRN) gene were recently described as the cause of ubiquitin positive frontotemporal dementia (FTD) in many families. Different frequencies of these genetic changes have been reported in diverse populations leading us to determine if these mutations were a major cause of FTD in the Portuguese population. The entire coding sequence plus exon 0 of PGRN were sequenced in a consecutive series of 46 FTD/CBS Portuguese patients. Two mutations were found: a novel pathogenic insertion (p.Gln300GlnfsX61) and a previously described point variant (p.T182M) of unclear pathogenicity. Pathogenic mutations in the PGRN gene were found in one of the 36 probands studied (3% of the probands in our series) who had a corticobasal syndrome presentation, indicating that in the Portuguese population, mutations in this gene are not a major cause of FTD.
authors.affiliation: Laboratory of Neurogenetics, National Institute on Aging, NIH, Porter Neuroscience Center, Bethesda, Maryland 20852, USA. portalegrer@nia.nih.gov
authors.forename: Rita Joao
authors.initials: RJ
authors.lastname: Guerreiro
authors.forename: Isabel
authors.initials: I
authors.lastname: Santana
authors.forename: Jose Miguel
authors.initials: JM
authors.lastname: Bras
authors.forename: Tamas
authors.initials: T
authors.lastname: Revesz
authors.forename: Olinda
authors.initials: O
authors.lastname: Rebelo
authors.forename: Maria Helena
authors.initials: MH
authors.lastname: Ribeiro
authors.forename: Beatriz
authors.initials: B
authors.lastname: Santiago
authors.forename: Catarina Resende
authors.initials: CR
authors.lastname: Oliveira
authors.forename: Andrew
authors.initials: A
authors.lastname: Singleton
authors.forename: John
authors.initials: J
authors.lastname: Hardy
mesh_terms: D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000378:metabolism; D003704:Dementia / Q000235:genetics* / Q000378:metabolism; D005192:Family Health; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D011174:Portugal / Q000453:epidemiology; D000077153:Progranulins
chemical_list: D004268:DNA-Binding Proteins; C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins