亨廷顿病的基因诊断及家系分析  

Molecular Diagnosis of Huntington's Disease:an analysis of two large families

作　　者：曾溢滔[1] 陈美珏[1] 毛跃华[1] 任兆瑞[1] 王秀英[1] 许志大[1] 何曦[1] 黄淑帧[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

出　　处：《中华医学杂志》1995年第11期689-693,共5页National Medical Journal of China

基　　金：国家863高科技发展计划资助

摘　　要：为了对亨廷顿病进行早期准确基因诊断，作者应用限制性片段长度多态性连锁分析和巢式聚合酶链反应直接检测ＩＴ１５基因ＣＡＧ三核苷酸重复序列的技术，对徐州和浙江两大亨廷顿病（ＨＤ）家系，共８例患者和３９例高风险家庭成员进行了基因诊断。变性聚丙烯酰胺凝胶电泳、放射自显影和直接ＤＮＡ测序的分析结果表明，在所分析的正常ＩＴ１５基因中，（ＣＡＧ）ｎ拷贝数大多为１６，而突变ＩＴ１５基因（ＣＡＧ）ｎ拷贝数均大于４０，两者不重叠。３９例ＨＤ高风险者的症状前预测的结果为：有１１名为ＨＤ基因携带者。结果不仅表明ＩＴ１５基因的不稳定突变是导致中国人ＨＤ的遗传学基础，而且为该病的基因诊断、遗传咨询提供了科学资料。At present molecular techniques comprise a main resource in the early accurate diagnosis for Huntington's disease.We describe the molecular diagnosis for 8 HD patients and 39 risky family members in two large HD pedigrees by using G8 RFLP linkage analysis as well as direct detection of the expanded (CAG) repeat in IT15 gene with the nested PCR denaturing polyacrylamide gel electrophoretic autoradiography and direct DNA sequencing.The results showed that the normal IT15 alleles contained 13 to 26 CAG repeat but major in 16,while all the HD alleles had over 40 copies of(CAG)n.There was no overlap between the normal and affected alleles.The presymptomatic diagnosis of 39 family members at risk for HD disclosed that 11 subjects carried the affected alleles.All these results indicated that the unstable mutations in IT15 gene were responsible for HD in the Chinese.They also provide valuable data for HD molecular diagnosis,genetic counselling and genetic health.

关 键 词：HUNTINGTON病 遗传病 基因诊断 基因突变 

分 类 号：R596.04[医药卫生—内科学] R742.204[医药卫生—临床医学]