Characteristics of frontotemporal dementia patients with a Progranulin mutation
Article first published online: 18 SEP 2006
Copyright © 2006 American Neurological Association
Annals of Neurology
Volume 60, Issue 3, pages 374–380, September 2006
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
- Issue published online: 18 SEP 2006
- Article first published online: 18 SEP 2006
- Manuscript Revised: 7 AUG 2006
- Manuscript Accepted: 7 AUG 2006
- Manuscript Received: 28 JUL 2006
- 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
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.
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.
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.
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