title: Co-occurrence of the C9ORF72 expansion and a novel GRN mutation in a family with alternative expression of frontotemporal dementia and amyotrophic lateral sclerosis.
abstract: The C9ORF72 repeat expansion is the major cause of frontotemporal lobar degeneration (FTLD), amyotrophic lateral sclerosis (ALS), and FTLD-ALS. In the reported pedigree, the 47-year old proband, presenting a four-year history of frontotemporal dementia, carried the C9ORF72 expansion plus a novel GRN p.Cys246X mutation. The father and a paternal uncle, harboring the C9ORF72 expansion only, had died by pure ALS with onset at 63 and 76 years, respectively. The case report and a review of the literature emphasize that phenotypical variations of the FTLD-ALS spectrum could be due to digenic inheritance.
authors.affiliation: Section of Neuropathology, Department of Neurological and Movement Sciences, University of Verona, Verona, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Testi
authors.affiliation: Section of Clinical Neurology, Department of Neurological and Movement Sciences, University of Verona, Verona, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Tamburin
authors.affiliation: Neurology Section, Pederzoli Hospital, Peschiera del Garda, Verona, Italy.
authors.forename: Giampietro
authors.initials: G
authors.lastname: Zanette
authors.affiliation: Section of Neuropathology, Department of Neurological and Movement Sciences, University of Verona, Verona, Italy.
authors.forename: Gian Maria
authors.initials: GM
authors.lastname: Fabrizi
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D000073885:C9orf72 Protein; D005192:Family Health; D005260:Female; D019788:Fluorodeoxyglucose F18; D057180:Frontotemporal Dementia / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D049268:Positron-Emission Tomography; D000077153:Progranulins; D011506:Proteins / Q000235:genetics*
chemical_list: D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins; D011506:Proteins; D019788:Fluorodeoxyglucose F18
keywords: Amyotrophic lateral sclerosis (ALS); C9ORF72; FTLD-ALS; GRN; frontotemporal lobar degeneration (FTLD)