摘要
目的 探讨早老素-1 基因突变在散发性Alzheim er 病(sporadic Alzheim er's disease, SAD)患者发病机理中的作用。方法 应用聚合酶链反应-单链构象多态性(polym erase chain reaction-singlestrand conform ation polym orphsim ,PCR-SSCP)及DNA 直接测序技术检测68 例SAD 患者和65 名正常老年人的早老素-1 基因第5 外显子。结果 发现68 例SAD患者中有4 例患者的SSCP发生泳动异常,DNA 序列分析发现:这4 例SAD 患者的130 号密码子发生了CTG→ATG 错义突变(388 位点发生C→A突变),使氨基酸由亮氨酸变为蛋氨酸(Leu 130 Met);157 号密码子发生了GTG→CTG 错义突变(469 位点发生G→C突变),使氨基酸由缬氨酸变为亮氨酸(Val157 Leu);有11 例患者的SSCP表现为一条单链电泳迁移率明显增快,DNA 序列分析发现:这11 例SAD患者的130 号密码子发生了CTG→ATG 错义突变(388 位点发生C→A 突变),使氨基酸由亮氨酸变为蛋氨酸(Leu 130 Met);154 号密码子发生了TGC→TGT 同义突变(462 位点发生C→T)突变。结论 我们发现在SAD患者中存在早老素-1 基因第5 外显子突变,该突变点可能为中国人SAD 患者早老素基因突变点之一。
Objective To explore the role of the mutation of presenilin 1 in pathogenesis of sporadic Alzheimer's disease.Methods The exon 5 of presenilin 1 was analysed by using ploymerase chain reaction single strand conformation polymorphism(PCR SSCP) and ABI 310 genetic analyzer technique in 68 patients with Alzheimer's disease and 65 normal controls.Results A mobility shift of SSCP in exon 5 of presenilin 1 was detected in 4 patients with Alzheimer's disease;two missense mutations were found. One mutation was at Leu 130 Met and the other at Val157 Leu.Another mobility shift of SSCP in exon 5 of presenilin 1 was detected in 11 patients with Alzheimer's disease. One missense mutation was at Leu 130Met and one same sense mutation C462→T. But no mobility shift of SSCP was found in patients with vascular dementia and in normal controls.Conclusion The authors found that mutations in exon 5 of presenilin 1 also existed in patients with sporadic Alzheimer's disease, which might be one of the points of mutations in sporadic Alzheimer's disease in Chinese.
出处
《中华医学遗传学杂志》
CAS
CSCD
北大核心
1999年第6期349-352,共4页
Chinese Journal of Medical Genetics
基金
"九五"国家医学科技攻关项目资助
国家自然科学基金资助
