Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Original Research Article Dement Geriatr Cogn Disord 2009;28:239–243 DOI: 10.1159/000241876 Absence of TARDBP Gene Mutations in an Italian Series of Patients with Frontotemporal Lobar Degeneration Salvatore Gallone a Maria Teresa Giordana b Elio Scarpini d Innocenzo Rainero a Elisa Rubino a Pierpaola Fenoglio a Daniela Galimberti d Silvia Grifoni b Eliana Venturelli d Pier Luigi Acutis d Silvia Peletto d Maria Grazia Maniaci c Patrizia Ferrero a Michela Zotta a Lorenzo Pinessi a a Neurology II, Department of Neuroscience, and b Department of Neuroscience, University of Turin, and c Istituto Zooprofilattico Piemonte, Liguria e Valle d’Aosta, Turin, and d Department of Neurological Sciences, University of Milan, IRCCS Ospedale Maggiore Policlinico, Milan, Italy sion: Our study, in accord with previous studies in different populations, found no evidence for a major genetic role of the TARDBP gene in FTLD. Copyright © 2009 S. Karger AG, Basel Introduction Frontotemporal lobar degeneration (FTLD) is the name for a group of clinically, pathologically and genet- ically heterogeneous disorders associated with atrophy in the frontal and temporal lobes of the brain [1] . Fron- totemporal dementia (FTD) is the most common clini- cal subtype of FTLD. It is characterized by personality change and impaired social conduct. Semantic demen- tia, progressive nonfluent aphasia and progressive apraxia arise from different topographical distributions of similar underlying pathologies. Besides the cognitive and behavioral symptoms, FTLD can also be associated with motor neuron disease (MND) and extrapyramidal signs. In the age group below 65 years, FTLD is the second most common cause of dementia after Alzhei- Key Words Frontotemporal lobar degeneration  TAR DNA-binding protein 43  Gene mutation  Polymorphism Abstract Background/Aim: Recent studies showed that TAR DNA- binding protein 43 (TDP-43), encoded by the TARDBP gene, is a major pathological protein in both sporadic and familial frontotemporal lobar degeneration (FTLD). The aim of this study was to search for mutations of the TARDBP gene in the disease. Methods: We sequenced the TARDBP gene in 172 unrelated FTLD patients recruited from 2 Italian memory clinics. Results: We identified 3 different variants of the TARDBP gene in 12 FTLD patients. Three patients showed a silent variant, Ala66Ala (c.332T ] C) in exon 2. A novel het- erozygous mutation was found in intron 4 (c.543 + 51A ] G) in 1 patient, which is not located at the splicing site. Finally, a c.208C ] T variant in the 3  untranslated region was de- tected in 8 probands. None of the aforementioned variants were predicted to affect TDP-43. Hence, pathogenic muta- tions were not identified in any of the FTLD cases. Conclu- Accepted: August 7, 2009 Published online: September 25, 2009 Prof. Innocenzo Rainero Neurology II – Headache Center, Department of Neuroscience University of Turin, Via Cherasco 15 IT–10126 Turin (Italy) Tel. +39 011 663 8510, Fax +39 011 696 3487, E-Mail irainero @ molinette.piemonte.it © 2009 S. Karger AG, Basel 1420–8008/09/0283–0239$26.00/0 Accessible online at: www.karger.com/dem