title: Clinicopathologic variability of the GRN A9D mutation, including amyotrophic lateral sclerosis.
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.
authors.affiliation: Departments of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
authors.forename: Ashley
authors.initials: A
authors.lastname: Cannon
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Fujioka
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Rutherford
authors.forename: Tanis J
authors.initials: TJ
authors.lastname: Ferman
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Broderick
authors.forename: Kevin B
authors.initials: KB
authors.lastname: Boylan
authors.forename: Neill R
authors.initials: NR
authors.lastname: Graff-Radford
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Uitti
authors.forename: Rosa
authors.initials: R
authors.lastname: Rademakers
authors.forename: Zbigniew K
authors.initials: ZK
authors.lastname: Wszolek
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Dickson
mesh_terms: D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D001480:Basal Ganglia Diseases / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D001921:Brain / Q000473:pathology*; D005260:Female; D057180:Frontotemporal Dementia / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D000077153:Progranulins
chemical_list: C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins