title: Non Fluent Variant of Primary Progressive Aphasia Due to the Novel GRN g.9543delA(IVS3-2delA) Mutation.
abstract: Mutations in progranulin gene (GRN) are a common cause of autosomal dominant frontotemporal lobar degeneration syndromes and are associated with a wide phenotypic heterogeneity. The majority of genetic defects in GRN consists of loss-of-function mutations, causing haploinsufficiency, and is associated with extremely low plasma progranulin levels. Herein, we describe a patient who developed language dysfunctions and memory disturbances at 63 years of age. Considering the early onset and the positive family history (sister aged 50 with non-fluent/agrammatic variant of primary progressive aphasia, father with behavioral disturbances in his sixties), a genetic analysis was carried out, showing the presence of a novel mutation [g.9543delA (IVS3-2delA)] in a predicted splicing site of GRN. Her progranulin plasma levels were under the reference threshold, as in her sister, thus supporting the causative role of the new variant. The same genetic mutation was confirmed by sequencing in her sister. Results described enlarge current knowledge on genetic causes of the disease and clinical characteristics of carriers.
authors: Neurology Unit, Department of Pathophysiology and Transplantation, University of Milan, Fondazione Ca' Granda, IRCCS Ospedale Policlinico, Milan, Italy.
authors: Sara M G
authors: SM
authors: Cioffi
authors: Neurology Unit, Department of Pathophysiology and Transplantation, University of Milan, Fondazione Ca' Granda, IRCCS Ospedale Policlinico, Milan, Italy.
authors: Daniela
authors: D
authors: Galimberti
authors: Department of Neurosciences, University of Parma, Parma, Italy.|Center for Cognitive Disorders and Dementia (CDCD), AUSL, Parma, Italy.
authors: Federica
authors: F
authors: Barocco
authors: Department of Neurosciences, University of Parma, Parma, Italy.|Center for Cognitive Disorders and Dementia (CDCD), AUSL, Parma, Italy.
authors: Marco
authors: M
authors: Spallazzi
authors: Neurology Unit, Department of Pathophysiology and Transplantation, University of Milan, Fondazione Ca' Granda, IRCCS Ospedale Policlinico, Milan, Italy.
authors: Chiara
authors: C
authors: Fenoglio
authors: Neurology Unit, Department of Pathophysiology and Transplantation, University of Milan, Fondazione Ca' Granda, IRCCS Ospedale Policlinico, Milan, Italy.
authors: Maria
authors: M
authors: Serpente
authors: Neurology Unit, Department of Pathophysiology and Transplantation, University of Milan, Fondazione Ca' Granda, IRCCS Ospedale Policlinico, Milan, Italy.
authors: Marina
authors: M
authors: Arcaro
authors: Department of Neurosciences, University of Parma, Parma, Italy.|Center for Cognitive Disorders and Dementia (CDCD), AUSL, Parma, Italy.
authors: Simona
authors: S
authors: Gardini
authors: Neurology Unit, Department of Pathophysiology and Transplantation, University of Milan, Fondazione Ca' Granda, IRCCS Ospedale Policlinico, Milan, Italy.
authors: Elio
authors: E
authors: Scarpini
authors: Department of Neurosciences, University of Parma, Parma, Italy.|Center for Cognitive Disorders and Dementia (CDCD), AUSL, Parma, Italy.
authors: Paolo
authors: P
authors: Caffarra
mesh_terms: D018888:Aphasia, Primary Progressive / Q000097:blood / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D000077153:Progranulins
chemical_list: C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins
keywords: Deletion; frontotemporal dementia; haploinsufficiency; mutation; non-fluent variant primary progressive aphasia; progranulin (GRN); splicing