PRNP P39L Variant is a Rare Cause of Frontotemporal Dementia in Italian Population

Article type: Short Communication

Authors: Oldoni, Emanuela^{a; 1} | Fumagalli, Giorgio G.^{a; 1} | Serpente, Maria^a | Fenoglio, Chiara^a | Scarioni, Marta^a | Arighi, Andrea^a | Bruno, Giuseppe^b | Talarico, Giuseppina^b | Confaloni, Annamaria^c | Piscopo, Paola^c | Nacmias, Benedetta^d | Sorbi, Sandro^d | Rainero, Innocenzo^e | Rubino, Elisa^e | Pinessi, Lorenzo^e | Binetti, Giuliano^f | Ghidoni, Roberta^f | Benussi, Luisa^f | Grande, Giulia^g | Arosio, Beatrice^h | Bursey, Devanⁱ | Kauwe, John S.ⁱ | Cioffi, Sara MG^a | Arcaro, Marina^a | Mari, Daniela^h | Mariani, Claudio^g | 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] University “Sapienza”, Rome, Italy | [c] Istituto Superiore di Sanitá, Rome, Italy | [d] Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Italy | [e] Neurology I, Department of Neuroscience, Department of Neuroscience, University of Torino, Italy | [f] Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy | [g] Center for Research and Treatment of Cognitive Dysfunctions, Institute of Clinical Neurology, Department of Biomedical and Clinical Sciences, “Luigi Sacco” Hospital, University of Milan, Milan, Italy | [h] Geriatric Unit, Department of Medical Sciences and Community Health, University of Milan, Fondazione Ca’ Granda, IRCCS Ospedale Policlinico, Milan, Italy | [i] Department of Biology, Brigham Young University, Provo, UT, USA

Correspondence: [*] Correspondence to: Daniela Galimberti, Neurology Unit, Department of Pathophysiology and Transplantation, University of Milan, Fondazione Ca’ Granda, IRCCS Ospedale Policlinico, Milan, Italy. Tel.: +39 0255033847; Fax: +39 0255036580; E-mail: [email protected].

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

Abstract: The missense P39L variant in the prion protein gene (PRNP) has recently been associated with frontotemporal dementia (FTD). Here, we analyzed the presence of the P39L variant in 761 patients with FTD and 719 controls and found a single carrier among patients. The patient was a 67-year-old male, with a positive family history for dementia, who developed apathy, short term memory deficit, and postural instability at 66. Clinical and instrumental workup excluded prion disease. At MRI, bilateral frontal lobe atrophy was present. A diagnosis of FTD was made, with a mainly apathetic phenotype. The PRNP P39L mutation may be an extremely rare cause of FTD (0.13%).

Keywords: Frontotemporal dementia, mutation, P39L, prion, PRNP

DOI: 10.3233/JAD-150863

Journal: Journal of Alzheimer's Disease, vol. 50, no. 2, pp. 353-357, 2016