% % 0期刊文章% Shinsuke Fujioka大炮阿什利%一个莎林Traynor %尼古拉·卢瑟福%坦尼斯Ferman %一个凯文Boylan丹尼尔·布罗德里克% %尼尔Graff-Radford % Ryan Uitti %罗莎说Rademakers %一个丹尼斯·迪克森兹比格涅夫•Wszolek % % T临床病理的变化入库单A9D突变,包括肌萎缩性脊髓侧索硬化症(P05.077) % D J神经病学2013% % P P05.077-P05.077 % V 80% N %首页 X 7补充目的:我们研究了入库单的临床和病理表型与致病性突变携带者A9D g.26C >一个错义突变。背景:入库单基因突变的最常见原因是额颞叶大叶性变性(FTLD)。额颞叶痴呆行为变体(bvFTD)和原发性进行性失语是最常见的临床表现。入库单突变很少与FTLD与运动神经元疾病,但没有报告的肌萎缩性脊髓侧索硬化症(ALS)由于致病性入库单突变。病理上,大多数入库单突变携带者TDP-43病理类型。大多数的入库单突变促进过早终止编码序列,从而导致haploinsufficiency由于nonsense-mediated RNA衰变。一个例外是A9D (g.26C >)错义突变,导致haploinsufficiency由于入库单分泌的损失。设计/方法:三个入库单A9D突变患者临床评估和后续neuropathologic来解剖检查。结果:入库单A9D突变患者的临床诊断ALS,非典型锥体束外的障碍,和bvFTD。TDP-43病理形态和分布变量,与著名的脊髓运动神经元参与与ALS患者呈现。TDP-43形态符合类型在所有但ALS的情况下,B型。结论:临床表现的入库单A9D错义突变与bvFTD高度可变,只是偶尔出现,这是典型的对其他致病入库单突变。 Importantly, we report for the first time that a GRN mutation can be associated with clinical and pathologic features ALS.Supported by: ZKW, RJU, and DWD are partially supported by the NIH/NINDS Morris K. Udall center awarded to the Mayo Clinic Jacksonville, P50 NS072187-01S2.Disclosure: Dr. Fujioka has nothing to disclose. Dr. Ashley has nothing to disclose. Dr. Traynor has nothing to disclose. Dr. Rutherford has nothing to disclose. Dr. Ferman has nothing to disclose. Dr. Broderick has nothing to disclose. Dr. Boylan has received research support from Biogen Idec, Cytokinetics, Inc., and Neuraltus Pharmaceuticals, Inc. Dr. Graff-Radford has received personal compensation for activities with Codman. Dr. Graff-Radford has received personal compensation in an editorial capacity for the Neurologist. Dr. Graff-Radford has received research support from Janssen, Pfizer Pharmaceuticals, Medivation, Forrest, and Allon. Dr. Uitti has received personal compensation in an editorial capacity for Neurology. Dr. Uitti has received research support from NINDS, Mayo Clinic, and St. Jude Medical. Dr. Rademakers has nothing to disclose. Dr. Wszolek has received personal compensation in an editorial cqapacity for Parkinsonism and Related Disorders and the European Journal of Neurology. Dr. Wszolek has received research support from the NIH/NINDS, Mayo Clinical Florida Research Committee CR Program, and Dystonia Medical Research Foundation. Dr. Dickson has received personal compensation for activities with Neotope, Inc. as a consultant.Wednesday, March 20 2013, 2:00 pm-7:00 pm %U