title: Novel missense progranulin gene mutation associated with the semantic variant of primary progressive aphasia.
abstract: Progranulin (GRN) mutations are typically associated with the behavioral variant of frontotemporal dementia and the non-fluent variant of primary progressive aphasia phenotypes. Hereby, we describe a patient affected by semantic variant of primary progressive aphasia (svPPA) with a highly positive family history of dementia, carrying a novel GRN missense variation in exon 11 [g.2897 C > T (p.Thr409Met)], predicted in silico to be damaging to protein structure and function. The variant was absent in 175 frontotemporal lobar degeneration (FTLD) patients and in 38 healthy subjects. This case confirms that GRN represents one of the most frequent FTLD genetic causes, suggesting that a screening is indicated in the case of svPPA presentation.
authors.affiliation: Neurorehabilitation Unit, Department of Clinical Neurosciences, San Raffaele Scientific Institute and Università Vita-Salute San Raffaele, Via Olgettina 60, Milan, Italy. cerami.chiara@hsr.it
authors.forename: Chiara
authors.initials: C
authors.lastname: Cerami
authors.forename: Alessandra
authors.initials: A
authors.lastname: Marcone
authors.forename: Daniela
authors.initials: D
authors.lastname: Galimberti
authors.forename: Chiara
authors.initials: C
authors.lastname: Villa
authors.forename: Chiara
authors.initials: C
authors.lastname: Fenoglio
authors.forename: Elio
authors.initials: E
authors.lastname: Scarpini
authors.forename: Stefano F
authors.initials: SF
authors.lastname: Cappa
mesh_terms: D018888:Aphasia, Primary Progressive / Q000235:genetics*; D057174:Frontotemporal Lobar Degeneration / Q000235:genetics; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D000077153:Progranulins
chemical_list: C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins