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Clinicopathologic features of frontotemporal dementia with Progranulin sequence variation

Spina, Salvatore and Murrell, Jill R. and Huey, Edward D. and Wassermann, Eric M. and Pietrini, Pietro and Baraibar, M.A. and Barbeito, A.G. and Troncoso, J.C. and Vidal, R. and Ghetti, Bernardino and Grafman, Jordan Clinicopathologic features of frontotemporal dementia with Progranulin sequence variation. Neurology, 68 (11). pp. 820-827. ISSN 0028-3878 (2007)

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Background: Frontotemporal lobar degeneration with ubiquitin-immunoreactive (ub-ir) inclusions (FTLD-U) has been associated with frontotemporal dementia (FTD) and ALS. Recently, mutations in Progranulin (PGRN), predicted to cause premature truncation of the PGRN coding sequence, were found in patients with inherited FTLD-U and ub-ir neuronal intranuclear inclusions (NII).Objective: To describe clinical, pathologic, and genetic features of three FTD patients having either a family history of FTD (A.III.1 and B.II.1) or of ALS (C.III.1).Methods: Patients underwent a single clinical assessment, MRI, and 18Ffluorodeoxyglucose PET brain scan. Neuropathologic examination and genetic analyses were carried out.Results: Patients presented clinically with the behavioral variant of FTD. Language dysfunctions were marked with comprehension being particularly affected. Neuroimaging revealed frontotemporal atrophy and glucose hypometabolism, with predominant left-side involvement, in Patients A.III.1 and B.II.1. Subject C.III.1 displayed mild atrophy and symmetric anterior hypometabolism. All patients were neuropathologically diagnosed with FTLD-U. Ub-ir NII were noted in Patients A.III.1 and B.II.1 but were absent in Patient C.III.1. The following PGRN sequence variations were found: IVS6-2A→G (A.III.1), R493X (B.II.1), and R433W (C.III.1). IVS6-2A→G may lead to skipping of exon 7 with consequent frameshift of the coding sequence and premature termination of PGRN translation.Conclusions: We have found two PGRN mutations associated with FTD, in affected individuals who are members of families with possible autosomal dominant FTD. A third PGRN sequence variation (R433W) was found in an FTD patient with family history of ALS.

Item Type: Article
Identification Number: 10.​1212/​01.​wnl.​0000254460.​31273.​2d
Subjects: R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Research Area: Computer Science and Applications
Depositing User: Caterina Tangheroni
Date Deposited: 22 Feb 2016 12:17
Last Modified: 06 Apr 2016 09:54
URI: http://eprints.imtlucca.it/id/eprint/3111

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