TY  - JOUR
Y1  - 2007///
TI  - Clinicopathologic features of frontotemporal dementia with Progranulin sequence variation
AV  - none
IS  - 11
JF  - Neurology
UR  - http://www.neurology.org/content/68/11/820.abstract
PB  - Lippincott Williams & Wilkins
SN  - 0028-3878
A1  - Spina, Salvatore
A1  - Murrell, Jill R.
A1  - Huey, Edward D.
A1  - Wassermann, Eric M.
A1  - Pietrini, Pietro
A1  - Baraibar, M.A.
A1  - Barbeito, A.G.
A1  - Troncoso, J.C.
A1  - Vidal, R.
A1  - Ghetti, Bernardino
A1  - Grafman, Jordan
SP  - 820
N2  - 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.
ID  - eprints3111
EP  - 827
VL  - 68
ER  -