TY - JOUR
T1 - Clinicopathologic variability of the GRN A9D mutation, including amyotrophic lateral sclerosis
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.
PY - 2013/5/7
Y1 - 2013/5/7
N2 - 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.
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.
UR - http://www.scopus.com/inward/record.url?scp=84879092067&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84879092067&partnerID=8YFLogxK
U2 - 10.1212/WNL.0b013e3182919059
DO - 10.1212/WNL.0b013e3182919059
M3 - Article
C2 - 23596077
AN - SCOPUS:84879092067
SN - 0028-3878
VL - 80
SP - 1771
EP - 1777
JO - Neurology
JF - Neurology
IS - 19
ER -