摘要
目的探讨早老素－１基因突变在散发性阿尔茨海默病（ＳｐｏｒａｄｉｃＡｌｚｈｅｉｍｅｒ′ｓｄｉｓｅａｓｅ，ＳＡＤ）患者发病机制中的作用。方法应用聚合酶链反应－单链构像多态性（ＰＣＲ－ＳＳＣＰ）及ＤＮＡ直接测序技术检测６８名ＳＡＤ患者、１３名血管性痴呆（ＶＤ）患者和６５名正常老年人的早老素－１基因第５号外显子。结果发现４名ＳＡＤ患者的ＰＣＲ产物ＳＳＣＰ分析发生泳动异常，ＤＮＡ序列分析发现：这４名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），使编码的氨基酸由亮氨酸变为蛋氨酸（Ｌｅｕ１３０Ｍｅｔ）；１５７号密码子发生了ＧＴＧ→ＣＴＧ错义突变（４６９位点发生Ｇ→Ｃ突变），使编码的氨基酸由缬氨酸变为亮氨酸（Ｖａｌ１５７Ｌｅｕ），另有１１名患者ＳＳＣＰ表现为一条单链增快，其性质待定。结论ＳＡＤ患者也存在早老素－１基因第５号外显子突变，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 Alzhemier's disease. Methods Exon 5 of presenilin-1
was analysed by using polymerase chain reaction-single strand conformation polymorphism
(PCR SSCP) and ABI 310 genetic analyzer technique in 68 patients with Alzheimer's disease,
13 patients with vascular dementia and 65 normal controls. Results Mobiligy shifts of SSCP in
exon 5 of presenilin-1 was detected in 4 cases with Alzheimer's disease. Two missense
mutation were found in the patients by DNA sequence analyse, one mutation was Leu 130 Met
and the other was Vall 57 Leu.Another 11 patients showed one single strend shifted rapidly.
But none mobility shifts of SSCP were found in patients with vascular dementia and normal
controls. Conclusions It is shown that mutations in exon 5 of presenilin 1 also exist in the
patients with sporadic Alzhemers disease, it might be one of the point mutation in sporadic
Alzhemer's disease of Chinese people.
出处
《中国神经精神疾病杂志》
CAS
CSCD
北大核心
1999年第3期142-144,共3页
Chinese Journal of Nervous and Mental Diseases
基金
"九五"国家医学科技攻关项目资助
国家自然科学基金
