Clinicopathologic variability of the GRN A9D mutation, including amyotrophic lateral sclerosis

Academic Article

Abstract

  • Objective: We examined the clinical and pathologic phenotypes of GRN mutation carriers with the pathogenic A9D (g.26C>A) missense mutation. Methods: Three patients with GRN A9D mutations were evaluated clinically and came to autopsy with subsequent neuropathologic examination. Results: The clinical diagnoses of patients with GRN A9D mutations were amyotrophic lateral sclerosis, atypical extrapyramidal disorder, and behavioral variant frontotemporal dementia. Immunohistochemistry for TAR DNA-binding protein 43 (TDP-43) revealed variability in morphology and distribution of pathology. One patient had notable involvement of motor neurons in the spinal cord as well as type B TDP-43, whereas 2 other patients had type A TDP-43. Conclusions: The clinical presentation of the GRN A9D missense mutation is not restricted to behavioral variant frontotemporal dementia and may include aphasia, extrapyramidal features, and, notably, amyotrophic lateral sclerosis. © 2013 American Academy of Neurology.
  • Authors

    Published In

  • Neurology  Journal
  • Digital Object Identifier (doi)

    Author List

  • Cannon A; Fujioka S; Rutherford NJ; Ferman TJ; Broderick DF; Boylan KB; Graff-Radford NR; Uitti RJ; Rademakers R; Wszolek ZK
  • Start Page

  • 1771
  • End Page

  • 1777
  • Volume

  • 80
  • Issue

  • 19