家族性阿尔茨海默病早老素-1基因突变位点的检测

目的：探讨早老素－1基因突变在家族性阿尔茨海默病（FAD）发病中的作用。方法：应用聚合酶链反应－单链构象多态性（PCR－SSCP）、变性高效液相（DHPLC）及DNA直接测序技术检测技术,对130人的阿尔茨海默病（AD）家系和50例正常对照组的早老素－1（PS－1）基因第4、5外显子进行了检测。结果：在早老素基因的第5外显子上发现除5例AD患者外,还有4例家系内正常人（Ⅳ－30、37、41、43）PCR－SSCP出现泳动异常。DHPLC检测进一步验证以上9例均表现双峰,提示可能有突变存在。DNA序列分析表明,这9例的早老素－1基因第5外显子的136号密码子发生了GCT→GGT错义突变,使氨基酸由丙氨酸变为甘氨酸（Ala136Gly);第4外显子未发现突变。家系内其他人及正常对照组的PS1基因第4、5外显子经以上检测均未发现异常。结论：PS1基因第5外显子的突变点可能为中国FAD患者早老素基因突变位点之一。

Mutation site of presenilin-1 gene in familial Alzheimer's disease

Objective To explore the effect of mutation of presenilin 1 (PS 1) gene on the pathogenesis of familial Alzheimer disease (FAD). Methods Polymerase chain reaction single strand conformation polymorphism (PCR SSCP), denaturing high performance liquid chromatography (DHPLC), and DNA sequencing were used to detect the exons 4 and 5 of PS 1 gene of a 130 member family and a 50 member control group. Result PCR SSCP showed abnormality in PS 1 exon 5 among 5 AD patients and 4 AD family members without AD symptoms. DHPLC further showed double peaks in the electrophoretic curves of the above nine persons, indicating the possibility of mutation. DNA sequencing revealed a missense mutation of GCT to GGT in code 136 of PS 1 exon 5, leading to the substitution of Ala with Gly (Ala136Gly), in these 9 persons. No mutation in exon 4 was found among these subjects. Mutation in exon 4 and 5 was not found in other members of both this AD family and the control group. Conclusion The mutation in exon 5 of PS 1 gene, found in this AD family, may be one of the responsible PS 1 gene mutations for familial Alzheimer disease in Chinese.