Departments of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Neurology. 2013 May 7;80(19):1771-7. doi: 10.1212/WNL.0b013e3182919059. Epub 2013 Apr 17.
We examined the clinical and pathologic phenotypes of GRN mutation carriers with the pathogenic A9D (g.26C>A) missense mutation.
Three patients with GRN A9D mutations were evaluated clinically and came to autopsy with subsequent neuropathologic examination.
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.
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.
我们研究了携带致病性 GRN 突变 A9D（g.26C>A）错义突变的患者的临床和病理表型。
对 3 名携带 GRN A9D 突变的患者进行了临床评估，并进行了尸检和随后的神经病理学检查。
GRN A9D 突变患者的临床诊断为肌萎缩侧索硬化症、非典型锥体外系疾病和行为变异额颞叶痴呆。针对 TAR DNA 结合蛋白 43（TDP-43）的免疫组织化学显示出病理学形态和分布的可变性。一名患者的脊髓运动神经元以及 B 型 TDP-43 显著受累，而另外 2 名患者则为 A 型 TDP-43。
GRN A9D 错义突变的临床表现不仅限于行为变异额颞叶痴呆，还可能包括失语症、锥体外系特征，以及显著的肌萎缩侧索硬化症。
