J Neurol Neurosurg Psychiatry 78:754-756 doi:10.1136/jnnp.2006.109553
  • Short report

Progranulin mutations and amyotrophic lateral sclerosis or amyotrophic lateral sclerosis–frontotemporal dementia phenotypes

  1. J C Schymick1,*,
  2. Y Yang2,*,
  3. P M Andersen3,*,
  4. J P Vonsattel4,
  5. M Greenway5,
  6. P Momeni1,
  7. J Elder1,
  8. A Chiò6,
  9. G Restagno7,
  10. W Robberecht8,
  11. C Dahlberg3,
  12. O Mukherjee9,
  13. A Goate9,
  14. N Graff-Radford10,
  15. R J Caselli11,
  16. M Hutton12,
  17. J Gass12,
  18. A Cannon12,
  19. R Rademakers12,
  20. A B Singleton1,
  21. O Hardiman5,
  22. J Rothstein2,
  23. J Hardy1,
  24. B J Traynor13
  1. 1Laboratory of Neurogenetics, National Institute of Aging, NIH, Bethesda, Maryland, USA
  2. 2Department of Neurology and Neuroscience, Johns Hopkins University, Baltimore, Maryland, USA
  3. 3Department of Neurology and Clinical Neuroscience, Umeå University Hospital, Umeå, Sweden
  4. 4Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, and Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, New York, USA
  5. 5Department of Neurology, Beaumont Hospital and Royal College of Surgeons in Ireland, Dublin, Ireland
  6. 6Department of Neuroscience, University of Torino, Torino, Italy
  7. 7Molecular Genetics Unit, Department of Clinical Pathology, Children’s Hospital, Torino, Italy
  8. 8Laboratory of Neurobiology, University of Leuven, Campus Gasthuisberg, Leuven, Belgium
  9. 9Washington University Alzheimer’s Disease Research Center, Washington University School of Medicine, St Louis, Missouri, USA
  10. 10Department of Neurology, Mayo Clinic College of Medicine, Jacksonville, Florida, USA
  11. 11Department of Neurology, Mayo Clinic Scottsdale, Arizona, USA
  12. 12Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, Florida, USA
  13. 13Section on Developmental Genetic Epidemiology, National Institute of Mental Health, Bethesda, Maryland, USA
  1. Correspondence to:
 Bryan J Traynor
 Porter Neuroscience Building, Room 1A-1014, 35 Convent Drive, Bethesda, MD 20892, USA; traynorb{at}
  • Received 21 October 2006
  • Accepted 7 March 2007
  • Revised 26 January 2007
  • Published Online First 19 March 2007


Objective: Mutations in the progranulin (PGRN) gene were recently described as the cause of ubiquitin positive frontotemporal dementia (FTD). Clinical and pathological overlap between amyotrophic lateral sclerosis (ALS) and FTD prompted us to screen PGRN in patients with ALS and ALS–FTD.

Methods: The PGRN gene was sequenced in 272 cases of sporadic ALS, 40 cases of familial ALS and in 49 patients with ALS–FTD.

Results: Missense changes were identified in an ALS–FTD patient (p.S120Y) and in a single case of limb onset sporadic ALS (p.T182M), although the pathogenicity of these variants remains unclear.

Conclusion:PGRN mutations are not a common cause of ALS phenotypes.


  • * J C Schymick, Y Yang and P M Andersen contributed equally to this work

  • Published Online First 19 March 2007

  • Competing interests: None.

    Funding: This research was supported (in part) by the Intramural Program of the NIA, NIMH and NINDS. RR is a postdoctoral fellow of the Fund for Scientific Research Flanders (FWO), Belgium.

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