中国内地散发性肌萎缩侧索硬化患者9号染色体开放阅读框72基因六核苷酸重复片段异常扩增及其临床表型  

Association between chromosome 9 open reading frame 72 hexanucleotide repeat expansions and clinical phenotypes in the sporadic amyotrophic lateral sclerosis population from China's Mainland

作　　者：唐璐[1] 刘蓉[1] 蔡宾[1] 刘晓鲁[1] 叶珊[1] 马妍[1] 张华纲[1] 崔德华[2] 樊东升[1] 

机构地区：[1]北京大学第三医院神经内科,100191 [2]北京大学神经科学研究所

出　　处：《中华神经科杂志》2013年第7期443-447,共5页Chinese Journal of Neurology

基　　金：国家自然科学基金资助项目（81030019）;北京市自然科学基金资助项目（7102161）;教育部博士点基金资助项目（20100001110084）;国家科技重大专项资助项目（2011ZX09307-001）

摘　　要：目的通过检测中国内地散发性肌萎缩侧索硬化（sALS）患者9号染色体开放阅读框72（C90RF72）基因六核苷酸（GGGGCC）重复片段异常扩增的发生率，探讨其在中国内地sALS患者遗传背景中的作用，分析该重复片段异常扩增与临床表型之间的关联。方法收集401例确诊和拟诊级别sALS患者的DNA样本和临床资料，经荧光片段长度检测和重复引物PCR方法，检测DNA样本的C90RF72基因六核苷酸（GGGGCC）重复片段扩增情况。结果共检出3例患者（0．7％，3／401）携带C90RF72基因六核苷酸（GGGGCC）重复片段异常扩增，均为男性，发病年龄54～58岁，均以上肢无力起病，后延髓受累，病程15—40个月。未携带该重复片段异常扩增的398例患者六核苷酸（GGGGCC）重复片段的平均重复数为3．54±2．62（2—14）。结论中国内地sALS患者中存在C90RF72基因六核苷酸（GGGGCC）重复片段异常扩增，虽其发生率远低于欧美人群，但仍是我国sALS患者不容忽视的致病基因之一。Objective To identify the existence and distribution of chromosome 9 open reading frame 72 （C9ORF72） hexanucleotide （GGGGCC） repeat expansions as well as the mutation-related clinical phenotypes in the sporadic amyotrophic lateral sclerosis （sALS） population from China's Mainland. Methods Deoxyribonuclec （DNA） samples and clinical data of 401 sALS cases were collected during 2007--2012. Fluorescent fragment-length analysis and repeat-primed polymerase chain reaction （PCR） were applied to detect the pathological GGGGCC repeat expansions. Results The C9ORF72 mutation was found in 3 sALS patients （0. 7%, 3/401 ）. All of them were male, spinal-onset during age 54--58, later bulbar-involved. The disease durations were from 15---40 months. The average C9ORF72 GGGGCC repeat numbers in 398 sALS patients without the C9ORF72 mutation is 3.54±2. 62（range from 2 to 14）. Conclusion This study clearly illustrates the existence and importance of the C9ORF72 repeat expansions in sALS population from China's Mainland, though the incidence is much lower than that in western population.

关 键 词：肌萎缩侧索硬化 DNA重复序列扩增 表型 

分 类 号：R746.4[医药卫生—神经病学与精神病学]