家族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GGGGCC中度重复扩增研究  

Analysis of chromosome 9 open reading frame 72 intermediate hexanucleotide repeat expansions in familial amyotrophic lateral sclerosis population from China's Mainland

作　　者：刘蓉[1] 唐璐[1] 张楠[1] 樊东升[1] 

机构地区：[1]北京大学第三医院神经内科,100191

出　　处：《中华神经科杂志》2014年第7期487-490,共4页Chinese Journal of Neurology

基　　金：国家自然科学基金资助项目（81030019）

摘　　要：目的 检测中国内地家族性肌萎缩侧索硬化（fALS）患者9号染色体开放阅读框72（C9ORF72）基因六核苷酸（GGGGCC）中度重复扩增（重复数为20 ～ 30）的发生率,分析其临床表型并探讨C9ORF72基因中度重复对中国内地fALS患者的意义.方法 对2007-2013年就诊于北京大学第三医院的62例fALS患者进行临床资料收集并提取DNA,检测C9ORF72基因六核苷酸重复片段扩增数目,确定其中重复数为20～ 30的患者并对其家系进行研究,最后进行20个单核苷酸多态性位点（20-SNP）单倍型分析.结果 62例fALS患者中检出1例中等重复扩增者（1.61％,1/62）,重复数为24.从该患者家系中检出2例重复数为24的中等重复扩增者.3例患者的20-SNP基因型与20-SNP奠基者的单倍型一致.结论 发现中国内地首例C9ORF72基因六核苷酸重复数大于20的fALS患者.C9ORF72基因中度重复扩增对中国内地fALS患者也具有致病性,是中国内地fALS的致病相关基因.Objective To identify the existence of chromosome 9 open reading frame 72 （C9ORF72） intermediate hexanucleotide （GGGGCC） repeat expansions as well as the mutation-related clinical phenotypes in familial amyotrophic lateral sclerosis （fALS） population from China's Mainland.Methods DNA samples and clinical data of 62 fALS cases were collected,then the pathological GGGGCC repeat expansions were detected.Haplotype analysis for 20 single nucleotide polymorphisms （SNPs） was performed finally.Results The C9ORF72 intermediate repeat expansions were found in one fALS patient （1.61%,1/62）,and repeat number was 24.In addition,2 siblings of this fALS patient also had a 24 repeats allele.These 24 repeat alleles were associated with the pathogenic founder haplotype.Conclusions This study illustrates the existence of the C9ORF72 intermediate repeat expansions in fALS population from China's Mainland for the first time.An intermediate repeat length in C9ORF72 is related to fALS in China's Mainland.

关 键 词：肌萎缩侧索硬化 多态性 单核苷酸 单元型 疾病遗传易感性 

分 类 号：R744.8[医药卫生—神经病学与精神病学]