Prominent phenotypic variability associated with mutations in Progranulin

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. SmithRobert J. Ivnik, Ronald C. Petersen

Research output: Contribution to journalArticlepeer-review

147 Scopus citations


Mutations in progranulin (PGRN) are associated with frontotemporal dementia with or without parkinsonism. We describe the prominent phenotypic variability within and among eight kindreds evaluated at Mayo Clinic Rochester and/or Mayo Clinic Jacksonville in whom mutations in PGRN were found. All available clinical, genetic, neuroimaging and neuropathologic data was reviewed. Age of onset ranged from 49 to 88 years and disease duration ranged from 1 to 14 years. Clinical diagnoses included frontotemporal dementia (FTD), primary progressive aphasia, FTD with parkinsonism, parkinsonism, corticobasal syndrome, Alzheimer's disease, amnestic mild cognitive impairment, and others. One kindred exhibited maximal right cerebral hemispheric atrophy in all four affected individuals, while another had maximal left hemisphere involvement in all three of the affected. Neuropathologic examination of 13 subjects revealed frontotemporal lobar degeneration with ubiquitin-positive inclusions plus neuronal intranuclear inclusions in all cases. Age of onset, clinical phenotypes and MRI findings associated with most PGRN mutations varied significantly both within and among kindreds. Some kindreds with PGRN mutations exhibited lateralized topography of degeneration across all affected individuals.

Original languageEnglish (US)
Pages (from-to)739-751
Number of pages13
JournalNeurobiology of Aging
Issue number5
StatePublished - May 2009

Bibliographical note

Funding Information:
This research is supported by National Institute on Aging grants AG06786, AG16574, AG11378 and AG07216, and the Robert H. and Clarice Smith and Abigail Van Buren Alzheimer's Disease Research Program of the Mayo Foundation. RR is a postdoctoral fellow from the Fund for Scientific Research Flanders (FWO-F). We thank the Mayo Clinic Alzheimer's Disease Research Center staff for their assistance in evaluating the subjects. We particularly thank the members of these eight families for participating in neurodegenerative disease research.


  • FTDP-17
  • Frontotemporal dementia
  • MRI
  • PGRN
  • Progranulin


Dive into the research topics of 'Prominent phenotypic variability associated with mutations in Progranulin'. Together they form a unique fingerprint.

Cite this