家族性Alzheimer病淀粉样蛋白前体基因第16、17外显子的突变分析

目的:了解中国家族性Alzheimer病(familial Alzheimer disease,FAD)患者中21号染色体上淀粉样蛋白前体(amyloid precursor protein,APP)基因第16、17外显子的突变情况。方法:应用限制性片段长度多态性(restrictionfragment length polymorphism,RFLP)、聚合酶链反应-单链构象多态性(polymerase chain reaction-single strand con-formation polymorphsim,PCR-SSCP)及DNA直接测序技术,对两个FAD家系以及20例正常对照组进行了APP基因第16、17外显子检测。结果:全部家系成员及正常对照组经RFLP分析均存在EcoR Ⅰ酶切位点、BclⅠ消化后无Bcl Ⅰ多态性。经PCR-SSCP分析均未见异常泳动带。两个家系的全部成员及正常对照组经DNA序列分析也未见APP基因的缺失、插入和置换。结论:本研究中的两个家系中未发现APP基因第16、17外显子的突变,证实了APP基因突变所引起的FAD并不多见。

A study on mutation of 16 and 17 exon of APP gene in familial Alzheimer''''s disease

Objective: To investigate the point mutation on 16 and 17 exon of APP gene in Chinese familial Alzheimer disease (FAD). Methods: Restriction fragment length polymorphism(RFLP), polymerase chain reaction-single strand conformation polymorphsim (PCR-SSCP) and direct Sequencing DNA technique were used to identify the mutation in exon 16 and exon17 of APP gene of two AD family and a 20-person control group. Results: There was EcoR cleavage site with no Bel I polymorphism shown in'RFLP analysis in all members of FAD family and control group. No any mobility shift in PCR-SSCP and no any deletion build-in and permutation of APP gene in Sequencing DNA were found in FAD and control group. Conclusion: It suggests that the mutation is uncommon on 16 and 17 exon of APP gene in Chinese FAD from the results of this study.