OBJECTIVE: Mutations 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. METHODS: In 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. RESULTS: We 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. INTERPRETATION: Known 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.
OBJECTIVE: Mutations 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. METHODS: In 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. RESULTS: We 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. INTERPRETATION: Known 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.
Authors: S F Fabre; C Forsell; M Viitanen; M Sjögren; A Wallin; K Blennow; M Blomberg; C Andersen; L O Wahlund; L Lannfelt Journal: Exp Neurol Date: 2001-04 Impact factor: 5.330
Authors: S M Rosso; W Kamphorst; B de Graaf; R Willemsen; R Ravid; M F Niermeijer; M G Spillantini; P Heutink; J C van Swieten Journal: Brain Date: 2001-10 Impact factor: 13.501
Authors: R Rademakers; M Cruts; B Dermaut; K Sleegers; S M Rosso; M Van den Broeck; H Backhovens; J van Swieten; C M van Duijn; C Van Broeckhoven Journal: Mol Psychiatry Date: 2002 Impact factor: 15.992
Authors: A Kowalska; T Asada; K Arima; C Kumakiri; W Kozubski; K Takahashi; T Tabira Journal: Dement Geriatr Cogn Disord Date: 2001 Nov-Dec Impact factor: 2.959
Authors: Odity Mukherjee; Pau Pastor; Nigel J Cairns; Sumi Chakraverty; John S K Kauwe; Shantia Shears; Maria I Behrens; John Budde; Anthony L Hinrichs; Joanne Norton; Denise Levitch; Lisa Taylor-Reinwald; Michael Gitcho; P-H Tu; Lea Tenenholz Grinberg; Rajka M Liscic; Javier Armendariz; John C Morris; Alison M Goate Journal: Ann Neurol Date: 2006-09 Impact factor: 10.422
Authors: Matt Baker; Ian R Mackenzie; Stuart M Pickering-Brown; Jennifer Gass; Rosa Rademakers; Caroline Lindholm; Julie Snowden; Jennifer Adamson; A Dessa Sadovnick; Sara Rollinson; Ashley Cannon; Emily Dwosh; David Neary; Stacey Melquist; Anna Richardson; Dennis Dickson; Zdenek Berger; Jason Eriksen; Todd Robinson; Cynthia Zehr; Chad A Dickey; Richard Crook; Eileen McGowan; David Mann; Bradley Boeve; Howard Feldman; Mike Hutton Journal: Nature Date: 2006-07-16 Impact factor: 49.962
Authors: Sarah N Fontaine; Jonathan J Sabbagh; Jeremy Baker; Carlos R Martinez-Licha; April Darling; Chad A Dickey Journal: Cell Mol Life Sci Date: 2015-02-11 Impact factor: 9.261
Authors: Brendan J Kelley; Wael Haidar; Bradley F Boeve; Matt Baker; Neill R Graff-Radford; Thomas Krefft; Andrew R Frank; Clifford R Jack; Maria Shiung; David S Knopman; Keith A Josephs; Sotirios A Parashos; Rosa Rademakers; Mike Hutton; Stuart Pickering-Brown; Jennifer Adamson; Karen M Kuntz; Dennis W Dickson; Joseph E Parisi; Glenn E Smith; Robert J Ivnik; Ronald C Petersen Journal: Neurobiol Aging Date: 2007-10-18 Impact factor: 4.673
Authors: A Lladó; R Sánchez-Valle; R Reñé; M Ezquerra; M J Rey; E Tolosa; I Ferrer; J L Molinuevo Journal: J Neural Transm (Vienna) Date: 2007-04-10 Impact factor: 3.575
Authors: Johannes Carolus Magnus Schlachetzki; Klaus Schmidtke; Jan Beckervordersandforth; Wiktor Borozdin; Christian Wilhelm; Michael Hüll; Jürgen Kohlhase Journal: J Neurol Date: 2009-07-19 Impact factor: 4.849
Authors: Parastoo Momeni; Karen DeTucci; Richard E Straub; Daniel R Weinberger; Peter Davies; Jordan Grafman; John Hardy; Edward D Huey Journal: Neurocase Date: 2010-01-18 Impact factor: 0.881