GRN Thr272fs Clinical Heterogeneity: A Case with Atypical Late Onset Presenting with a Dementia with Lewy Bodies Phenotype

Article type: Short Communication

Authors: Arosio, Beatrice^{a; b; 1; *} | Abbate, Carlo^{a; 1} | Galimberti, Daniela^{c; d} | Rossi, Paolo Dionigi^a | Inglese, Silvia^c | Fenoglio, Chiara^{c; d} | Ridolfi, Elisa^{c; d} | Gussago, Cristina^b | Casati, Martina^a | Tedone, Enzo^b | Ferri, Evelyn^a | Serpente, Maria^{c; d} | Scarpini, Elio^{c; d} | Mari, Daniela^{a; b}

Affiliations: [a] Geriatric Unit, University of Milan, Fondazione Cá Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy | [b] Department of Medical Sciences and Community Health, University of Milan, Geriatrics, Milan, Italy | [c] Neurology Unit, “Dino Ferrari” Center, University of Milan, Fondazione Cá Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy | [d] Department of Pathophysiology and Transplantation, “Dino Ferrari” Center, University of Milan, Fondazione Cá Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy

Correspondence: [*] Correspondence to: Beatrice Arosio, Geriatric Unit, Department of Medical Sciences and Community Health, University of Milan, Fondazione Cá Granda, IRCCS Ospedale Maggiore Policlinico, Via Pace 9, 20122 Milan, Italy. Tel.: +39 02 5503 54 05; Fax: +39 02 50320735; E-mail: [email protected].

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

Abstract: We describe a case of late onset frontotemporal dementia carrying the g.1977_1980 delCACT (Thr272fs) mutation in progranulin (GRN) gene, characterized by a positive family history for dementia and a clinical phenotype resembling dementia with Lewy bodies. Symptoms included prominent visuospatial impairment, complex misidentification syndrome, visual zooptic hallucinations, hypersomnia, mental fluctuations, and signs of parkinsonism. The patient showed normal cerebrospinal fluid levels of amyloid-β, tau, and Ptau biomarkers, an asymmetric pattern of cerebral atrophy and hypoperfusion, and parietal hypometabolism. A major contributing factor to the diagnosis was the testing of plasmatic progranulin levels (extremely low), which prompted us to sequence GRN.

Keywords: GRN Thr272fs, frontotemporal dementia, phenotype, progranulin

DOI: 10.3233/JAD-130053

Journal: Journal of Alzheimer's Disease, vol. 35, no. 4, pp. 669-674, 2013