RT Journal Article SR Electronic T1 Clinicopathologic variability of the GRN A9D mutation, including amyotrophic lateral sclerosis JF Neurology JO Neurology FD Lippincott Williams & Wilkins SP 1771 OP 1777 DO 10.1212/WNL.0b013e3182919059 VO 80 IS 19 A1 Cannon, Ashley A1 Fujioka, Shinsuke A1 Rutherford, Nicola J. A1 Ferman, Tanis J. A1 Broderick, Daniel F. A1 Boylan, Kevin B. A1 Graff-Radford, Neill R. A1 Uitti, Ryan J. A1 Rademakers, Rosa A1 Wszolek, Zbigniew K. A1 Dickson, Dennis W. YR 2013 UL http://n.neurology.org/content/80/19/1771.abstract AB 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.ALS=amyotrophic lateral sclerosis; bvFTD=behavioral variant frontotemporal dementia; FTLD=frontotemporal lobar degeneration; GCI=glial cytoplasmic inclusions; GFAP=glial fibrillary acidic protein; IBA1=ionized calcium-binding adaptor molecule 1; NCI=neuronal cytoplasmic inclusions; TDP-43=TAR DNA-binding protein 43