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

Ashley Cannon, Shinsuke Fujioka, Nicola J. Rutherford, Tanis Jill Ferman, Daniel F. Broderick, Kevin B. Boylan, Neill R Graff Radford, Ryan J. Uitti, Rosa V Rademakers, Zbigniew K Wszolek, Dennis W Dickson

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)1771-1777
Number of pages7
JournalNeurology
Volume80
Issue number19
DOIs
StatePublished - May 7 2013

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Amyotrophic Lateral Sclerosis
Frontotemporal Dementia
Mutation
DNA-Binding Proteins
Missense Mutation
Y-Box-Binding Protein 1
Basal Ganglia Diseases
Aphasia
Motor Neurons
Autopsy
Spinal Cord
Immunohistochemistry
Pathology
Phenotype
Protein

ASJC Scopus subject areas

  • Clinical Neurology
  • Arts and Humanities (miscellaneous)

Cite this

Clinicopathologic variability of the GRN A9D mutation, including amyotrophic lateral sclerosis. / Cannon, Ashley; Fujioka, Shinsuke; Rutherford, Nicola J.; Ferman, Tanis Jill; Broderick, Daniel F.; Boylan, Kevin B.; Graff Radford, Neill R; Uitti, Ryan J.; Rademakers, Rosa V; Wszolek, Zbigniew K; Dickson, Dennis W.

In: Neurology, Vol. 80, No. 19, 07.05.2013, p. 1771-1777.

Research output: Contribution to journalArticle

Cannon, Ashley ; Fujioka, Shinsuke ; Rutherford, Nicola J. ; Ferman, Tanis Jill ; Broderick, Daniel F. ; Boylan, Kevin B. ; Graff Radford, Neill R ; Uitti, Ryan J. ; Rademakers, Rosa V ; Wszolek, Zbigniew K ; Dickson, Dennis W. / Clinicopathologic variability of the GRN A9D mutation, including amyotrophic lateral sclerosis. In: Neurology. 2013 ; Vol. 80, No. 19. pp. 1771-1777.
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