Late-onset frontotemporal dementia associated with a novel PGRN mutation

  • A. Lladó
  • R. Sánchez-Valle
  • R. Reñé
  • M. Ezquerra
  • M. J. Rey
  • E. Tolosa
  • I. Ferrer
  • J. L. Molinuevo
Short communication

Summary

We describe a new mutation in the PGRN gene (A303AfsX57) associated with late-onset frontotemporal dementia and with “cat’s eye” shaped intranuclear and cytoplasmatic ubiquitin immunoreactive inclusions in the neuropathological exam. The A303AfsX57 mutation is consistent with a nucleotide deletion in exon 8 (c908delC). This deletion causes a frameshift at codon 303 that introduces a premature termination codon (A303AfsX57).

Keywords: Frontotemporal lobar degeneration, PGRN, ubiquitin, neuronal intranuclear inclusions, frameshift mutation 

References

  1. Baker, M, Mackenzie, IR, Pickering-Brown, SM, Gass, J, Rademakers, R, Lindholm, C, Snowden, J, Adamson, J, Sadovnick, AD, Rollinson, S, Cannon, A, Dwosh, E, Neary, D, Melquist, S, Richardson, A, Dickson, D, Berger, Z, Eriksen, J, Robinson, T, Zehr, C, Dickey, CA, Crook, R, McGowan, E, Mann, D, Boeve, B, Feldman, H, Hutton, M 2006Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17Nature442916919CrossRefPubMedGoogle Scholar
  2. Cruts, M, Gijselinck, I, van der Zee, J, Engelborghs, S, Wils, H, Pirici, D, Rademakers, R, Vandenberghe, R, Dermaut, B, Martin, JJ, van Duijn, C, Peeters, K, Sciot, R, Santens, P, De Pooter, T, Mattheijssens, M, Van den Broeck, M, Cuijt, I, Vennekens, K, De Deyn, PP, Kumar-Singh, S, Van Broeckhoven, C 2006Null mutations in progranulin cause ubiquitinpositive frontotemporal dementia linked to chromosome 17q21Nature442920924CrossRefPubMedGoogle Scholar
  3. Gass, J, Cannon, A, Mackenzie, IR, Boeve, B, Baker, M, Adamson, J, Crook, R, Melquist, S, Kuntz, K, Petersen, R, Josephs, K, Pickering-Brown, SM, Graff-Radford, N, Uitti, R, Dickson, D, Wszolek, Z, Gonzalez, J, Beach, TG, Bigio, E, Johnson, N, Weintraub, S, Mesulam, M, White, CL,3rd, Woodruff, B, Caselli, R, Hsiung, GY, Feldman, H, Knopman, D, Hutton, M, Rademakers, R 2006Mutations in progranulin are a major cause of ubiquitin-positive frontotemporal lobar degenerationHum Mol Genet1529883001CrossRefPubMedGoogle Scholar
  4. 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 2006Characteristics of frontotemporal dementia patients with a Progranulin mutationAnn Neurol60374380CrossRefPubMedGoogle Scholar
  5. Neary, D, Snowden, JS, Gustafson, L, Passant, U, Stuss, D, Black, S, Freedman, M, Kertesz, A, Robert, PH, Albert, M, Boone, K, Miller, BL, Cummings, J, Benson, DF 1998Frontotemporal lobar degeneration. A consensus on clinical diagnostic criteriaNeurology5215461554Google Scholar
  6. Pickering-Brown, SM, Baker, M, Gass, J, Boeve, BF, Loy, CT, Brooks, WS, Mackenzie, IR, Martins, RN, Kwok, JB, Halliday, GM, Kril, J, Schofield, PR, Mann, DM, Hutton, M 2006Mutations in progranulin explain atypical phenotypes with variants in MAPTBrain12931243126CrossRefPubMedGoogle Scholar
  7. Rosso, SM, Donker Kaat, L, Baks, T, Joosse, M, de Koning, I, Pijnenburg, Y, de Jong, D, Dooijes, D, Kamphorst, W, Ravid, R, Niermeijer, MF, Verheij, F, Kremer, HP, Scheltens, P, van Duijn, CM, Heutink, P, van Swieten, JC 2003Frontotemporal dementia in The Netherlands: patient characteristics and prevalence estimates from a population-based studyBrain12620162022CrossRefPubMedGoogle Scholar
  8. Shi, J, Shaw, CL, Du Plessis, D, Bailey, KL, Julien, C, Stopford, C, Thompson, J, Varma, A, Craufurd, D, Tian, J, Pickering-Brown, S, Neary, D, Snowden, JS, Mann, DM 2005Histopathological changes underlying frontotemporal lobar degeneration with clinicopathological correlationActa Neuropathol11501512CrossRefGoogle Scholar
  9. Snowden, JS, Pickering-Brown, SM, Mackenzie, IR, Mackenzie, IR, Richardson, AM, Varma, A, Neary, D, Mann, DM 2006Progranulin gene mutations associated with frontotemporal dementia and progressive non-fluent aphasiaBrain12930913102CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • A. Lladó
    • 1
  • R. Sánchez-Valle
    • 1
  • R. Reñé
    • 2
  • M. Ezquerra
    • 3
  • M. J. Rey
    • 4
  • E. Tolosa
    • 3
  • I. Ferrer
    • 4
  • J. L. Molinuevo
    • 1
  1. 1.Alzheimer’s Disease and Cognitive Disorders Unit, Neurology ServiceHospital Clínic and Institut d’Investigació Biomèdica August Pi i Sunyer (IDIBAPS)BarcelonaSpain
  2. 2.Unitat de Diagnòstic i Tractament de les Demències, Servei de NeurologiaHospital Universitari de BellvitgeBarcelonaSpain
  3. 3.Parkinson’s Disease and Movement Disorders Unit, Neurology ServiceHospital Clínic and Institut d’Investigació Biomèdica August Pi i Sunyer (IDIBAPS)BarcelonaSpain
  4. 4.Brain BankUniversity of Barcelona/Hospital ClínicBarcelonaSpain

Personalised recommendations