PT  - JOURNAL ARTICLE
AU  - Cannon, Ashley
AU  - Fujioka, Shinsuke
AU  - Rutherford, Nicola J.
AU  - Ferman, Tanis J.
AU  - Broderick, Daniel F.
AU  - Boylan, Kevin B.
AU  - Graff-Radford, Neill R.
AU  - Uitti, Ryan J.
AU  - Rademakers, Rosa
AU  - Wszolek, Zbigniew K.
AU  - Dickson, Dennis W.
TI  - Clinicopathologic variability of the <em>GRN</em> A9D mutation, including amyotrophic lateral sclerosis
AID  - 10.1212/WNL.0b013e3182919059
DP  - 2013 May 07
TA  - Neurology
PG  - 1771--1777
VI  - 80
IP  - 19
4099  - http://n.neurology.org/content/80/19/1771.short
4100  - http://n.neurology.org/content/80/19/1771.full
SO  - Neurology2013 May 07; 80
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