中国人亨廷顿病CAG三核苷酸重复的分子分析  

MOLECULAR ANALYSIS OF HUNTINGTON'S DISEASE WITH EXPANDED CAG TRINUCLEOTIDE REPEAT IN CHINESE

作　　者：毛跃华[1] 周刚[1] 陈美珏[1] 任兆瑞[1] 王秀英[1] 叶文虎[1] 赵向智[1] 黄淑帧[1] 曾溢滔[1] 

机构地区：[1]上海市儿童医院上海医学遗传研究所,徐州医学院附属医院,安徽医科大学,河南省精神病医院

出　　处：《中华医学遗传学杂志》1996年第3期131-134,共4页Chinese Journal of Medical Genetics

基　　金：国家"863"高技术资助

摘　　要：为在分子水平了解中国人亨廷顿病的发病机理，为该病的基因诊断和遗传咨询提供科学依据，应用巢式ＰＣＲ、变性聚丙烯酰胺凝胶电泳以及ＤＮＡ测序等方法，对正常中国人及亨廷顿病（Ｈｕｎｔｉｎｇｔｏｎ＇ｓｄｉｓｅａｓｅ，ＨＤ）患者的ＩＴ１５基因（ＣＡＧ）ｎ重复序列的拷贝数进行了分析。４０例正常中国人以及１３个ＨＤ家系的研究结果表明：中国人正常ＩＴ１５基因（ＣＡＧ）ｎ重发序列的拷贝数为１３～２６，多数为１６；而所有被分析的ＨＤ患者都携带一个ＣＡＧ序列高度重复的ＩＴ１５基因，其（ＣＡＧ）ｎ的拷贝数为４０～９４；且ＣＡＧ重复序列的拷贝数与发病年龄呈现一定的相关性。正常和ＨＤ等位基因之间的（ＣＡＧ）ｎ拷贝数不相重叠，在１０３例高风险ＨＤ家庭成员的症状前诊断中，根据（ＣＡＧ）ｎ拷贝数的测定，发现了３５例ＨＤ基因携带者，结果表明，ＩＴ１５基因的不稳定突变是导致中国人亨廷顿病的遗传基础。This is a study on the pathogenesis of Huntington's disease(HD).The polymorphic CAG repeats in the IT15 gene in normal Chinese and HD patients were determined with nested PCR,denaturing polyacrylamide gel electrophoresis and direct sequencing analysis,A total of 40 normal individuals and 122 members of 13 unrelated HD families from Shanghai, Jiangsu, Zhejiang, Anhui, Shangdong, Guangdong and Henan, were included in this study. The results showed that the(CAG)n repeat numbers in 270 normal alleles ranged from 13 to 26 mostly 16 in number, while in 54 HD alleles,the number of CAG repeats was from 40 to 94, with an unstable inheritance of expanded repeats in some families, There was no overlap between the copy number of the normal and affected alleles. In addition, the presymptomatic diagnosis in 103 family members at risk for HD disclosed that 35 individuals had HD alleles. These findings suggest that the unstable mutation in IT15 gene be responsible for the genetic defect in Chinese HD patients and a correlation should exist between the number of (CAG)n repeats and the onset age of the disease.

关 键 词：亨廷顿病 IT15基因 基因突变 三核苷酸 重复 

分 类 号：R596.102[医药卫生—内科学]