Characteristics of frontotemporal dementia patients with a Progranulin mutation

Edward D. Huey, Jordan Grafman, Eric M. Wassermann, Pietro Pietrini, Michael C. Tierney, Bernardino Ghetti, Salvatore Spina, Matt Baker, Mike Hutton, Joshua W. Elder, Stephen L. Berger, Kyle A. Heflin, John Hardy, Parastoo Momeni

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Abstract

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.

Original languageEnglish
Pages (from-to)374-380
Number of pages7
JournalAnnals of Neurology
Volume60
Issue number3
DOIs
StatePublished - Sep 2006

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Frontotemporal Dementia
Mutation
Genes
Deoxyglucose
Positron-Emission Tomography
Atrophy
Magnetic Resonance Imaging
Chromosomes, Human, Pair 17
Neurofibrillary Tangles
Terminator Codon
Fathers

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Huey, E. D., Grafman, J., Wassermann, E. M., Pietrini, P., Tierney, M. C., Ghetti, B., ... Momeni, P. (2006). Characteristics of frontotemporal dementia patients with a Progranulin mutation. Annals of Neurology, 60(3), 374-380. https://doi.org/10.1002/ana.20969

Characteristics of frontotemporal dementia patients with a Progranulin mutation. / Huey, Edward D.; Grafman, Jordan; Wassermann, Eric M.; Pietrini, Pietro; Tierney, Michael C.; Ghetti, Bernardino; Spina, Salvatore; Baker, Matt; Hutton, Mike; Elder, Joshua W.; Berger, Stephen L.; Heflin, Kyle A.; Hardy, John; Momeni, Parastoo.

In: Annals of Neurology, Vol. 60, No. 3, 09.2006, p. 374-380.

Research output: Contribution to journalArticle

Huey, ED, Grafman, J, Wassermann, EM, Pietrini, P, Tierney, MC, Ghetti, B, Spina, S, Baker, M, Hutton, M, Elder, JW, Berger, SL, Heflin, KA, Hardy, J & Momeni, P 2006, 'Characteristics of frontotemporal dementia patients with a Progranulin mutation', Annals of Neurology, vol. 60, no. 3, pp. 374-380. https://doi.org/10.1002/ana.20969
Huey, Edward D. ; Grafman, Jordan ; Wassermann, Eric M. ; Pietrini, Pietro ; Tierney, Michael C. ; Ghetti, Bernardino ; Spina, Salvatore ; Baker, Matt ; Hutton, Mike ; Elder, Joshua W. ; Berger, Stephen L. ; Heflin, Kyle A. ; Hardy, John ; Momeni, Parastoo. / Characteristics of frontotemporal dementia patients with a Progranulin mutation. In: Annals of Neurology. 2006 ; Vol. 60, No. 3. pp. 374-380.
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AU - Grafman, Jordan

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AU - Tierney, Michael C.

AU - Ghetti, Bernardino

AU - Spina, Salvatore

AU - Baker, Matt

AU - Hutton, Mike

AU - Elder, Joshua W.

AU - Berger, Stephen L.

AU - Heflin, Kyle A.

AU - Hardy, John

AU - Momeni, Parastoo

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N2 - 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.

AB - 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.

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