eprintid: 3118
rev_number: 5
eprint_status: archive
userid: 72
dir: disk0/00/00/31/18
datestamp: 2016-02-26 09:51:25
lastmod: 2016-02-26 09:51:25
status_changed: 2016-02-26 09:51:25
type: article
metadata_visibility: show
creators_name: Huey, Edward D.
creators_name: Grafman, Jordan
creators_name: Wassermann, Eric M.
creators_name: Pietrini, Pietro
creators_name: Tierney, Michael C.
creators_name: Ghetti, Bernardino
creators_name: Spina, Salvatore
creators_name: Baker, Matt
creators_name: Hutton, Mike
creators_name: Elder, Joshua W.
creators_name: Berger, Stephen L.
creators_name: Heflin, Kyle A.
creators_name: Hardy, John
creators_name: Momeni, Parastoo
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creators_id: pietro.pietrini@imtlucca.it
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title: Characteristics of frontotemporal dementia patients with a Progranulin mutation
ispublished: pub
subjects: RC0321
divisions: CSA
full_text_status: none
abstract: ObjectiveMutations in the Progranulin gene (PGRN) recently have been discovered to be associated with frontotemporal dementia (FTD) linked to 17q21 without identified MAPT mutations. The range of mutations of PGRN that can result in the FTD phenotype and the clinical presentation of patients with PGRN mutations have yet to be determined.MethodsIn this study, we examined 84 FTD patients from families not known previously to have illness linked to chromosome 17 for identified PGRN and MAPT mutations and sequenced the coding exons and the flanking intronic regions of PGRN. We compared the prevalence, clinical characteristics, magnetic resonance imaging and 18-fluoro-deoxyglucose positron emission tomography results, and neuropsychological testing of patients with the PGRN R493X mutation with those patients without identified PGRN mutations.ResultsWe discovered a new PGRN mutation (R493X) resulting in a stop codon in two patients. This was the only PGRN mutation identified in our sample. The patients with the PGRN R493X mutation had a rapid illness course and had predominant right-sided atrophy and hypometabolism on magnetic resonance imaging and 18-fluoro-deoxyglucose positron emission tomography. The affected father of one of the patients with the PGRN R493X mutation showed frontal and temporal atrophy without neurofibrillary tangles on neuropathological examination.InterpretationKnown PGRN and MAPT mutations were rare and of similar prevalence in our sample (2 compared with 1/84). The patients with the PGRN R493X mutation had a clinical presentation comparable with other behavior-predominant FTD patients. The neuropathology of an affected family member of a patient with the PGRN R493X mutation appears not to be Alzheimer's disease.
date: 2006
publication: Annals of Neurology
volume: 60
number: 3
publisher: Wiley Subscription Services, Inc., A Wiley Company
pagerange: 374-380
id_number: 10.1002/ana.20969
refereed: TRUE
issn: 0364-5134
official_url: http://dx.doi.org/10.1002/ana.20969
citation:   Huey, Edward D. and Grafman, Jordan and Wassermann, Eric M. and Pietrini, Pietro and Tierney, Michael C. and Ghetti, Bernardino and Spina, Salvatore and Baker, Matt and Hutton, Mike and Elder, Joshua W. and Berger, Stephen L. and Heflin, Kyle A. and Hardy, John and Momeni, Parastoo  Characteristics of frontotemporal dementia patients with a Progranulin mutation.  Annals of Neurology, 60 (3).  pp. 374-380.  ISSN 0364-5134      (2006)