The Novel GRN g.1159_1160delTG Mutation is Associated with Behavioral Variant Frontotemporal Dementia

Article type: Research Article

Authors: Calvi, Alberto^{a; 1} | Cioffi, Sara M.G.^{a; 1} | Caffarra, Paolo^{b; c} | Fenoglio, Chiara^a | Serpente, Maria^a | Pietroboni, Anna M.^a | Arighi, Andrea^a | Ghezzi, Laura^a | Gardini, Simona^b | Scarpini, Elio^a | Galimberti, Daniela^{a; *}

Affiliations: [a] Neurology Unit, Department of Pathophysiology and Transplantation, University of Milan, Fondazione Ca' Granda, IRCCS Ospedale Policlinico, Milan, Italy | [b] Department of Neurosciences, University of Parma, Parma, Italy | [c] Center for Cognitive Disorders, AUSL, Parma, Italy

Correspondence: [*] Correspondence to: Daniela Galimberti, Neurology Unit, Department of Pathophysiology and Transplantation, University of Milan, Fondazione Ca' Granda, IRCCS Ospedale Policlinico, via F. Sforza, 35, 20122, Milan, Italy. Tel.: +390255033847; Fax: +390255036580; E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

Abstract: Mutations in progranulin gene (GRN) are a common cause of autosomal dominant frontotemporal lobar degeneration and are associated with a wide phenotypic heterogeneity. Here, we describe two probands with behavioral variant frontotemporal dementia with a novel mutation in this gene (1159_1160delTG). Both had a positive family history for dementia and showed atypical features at imaging. Their progranulin plasma levels were undetectable, and the mutation was not present in cDNA, suggesting haploinsufficiency. Progranulin levels were low even in asymptomatic carriers of the variant. Results described enlarge current knowledge on genetic causes of the disease and clinical characteristics of carriers.

Keywords: Deletion, frontotemporal dementia, haploinsufficiency, mutation, progranulin (GRN)

DOI: 10.3233/JAD-141380

Journal: Journal of Alzheimer's Disease, vol. 44, no. 1, pp. 277-282, 2015