Brief Communication

Characteristics of frontotemporal dementia patients with a Progranulin mutation

  1. Edward D. Huey MD1,
  2. Jordan Grafman PhD1,*,
  3. Eric M. Wassermann MD1,2,
  4. Pietro Pietrini MD, PhD1,3,
  5. Michael C. Tierney MA1,
  6. Bernardino Ghetti MD4,
  7. Salvatore Spina MD4,
  8. Matt Baker BS5,
  9. Mike Hutton PhD5,
  10. Joshua W. Elder BS6,
  11. Stephen L. Berger6,
  12. Kyle A. Heflin6,
  13. John Hardy PhD6,
  14. Parastoo Momeni PhD6

Article first published online: 18 SEP 2006

DOI: 10.1002/ana.20969

Issue

Annals of Neurology

Annals of Neurology

Volume 60, Issue 3, pages 374–380, September 2006

Additional Information

How to Cite

Huey, E. D., Grafman, J., Wassermann, E. M., Pietrini, P., Tierney, M. C., Ghetti, B., Spina, S., Baker, M., Hutton, M., Elder, J. W., Berger, S. L., Heflin, K. A., Hardy, J. and Momeni, P. (2006), Characteristics of frontotemporal dementia patients with a Progranulin mutation. Ann Neurol., 60: 374–380. doi: 10.1002/ana.20969

Author Information

  1. 1

    Cognitive Neuroscience Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD

  2. 2

    Brain Stimulation Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD

  3. 3

    Laboratory of Clinical Biochemistry and Molecular Biology, University of Pisa, Pisa, Italy

  4. 4

    Indiana Alzheimer Disease Center, Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN

  5. 5

    Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, FL

  6. 6

    Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD

*Cognitive Neuroscience Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Building 10, Room 5C205, MSC 1440, Bethesda, MD 20892-1440

Publication History

  1. Issue published online: 18 SEP 2006
  2. Article first published online: 18 SEP 2006
  3. Manuscript Revised: 7 AUG 2006
  4. Manuscript Accepted: 7 AUG 2006
  5. Manuscript Received: 28 JUL 2006

Funded by

  • Intramural Research Programs of the NIH (National Institute of Neurological Disorders and Stroke)
  • National Institute on Aging. Grant Number: PHS P30 AG10133
  • Department of Neurological and Behavioral Sciences, University of Siena, Siena, Italy

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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. Ann Neurol 2006;60:374–380

This article includes supplementary materials available via the Internet at http://www.interscience.wiley.com/jpages/0364-5134/suppmat

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