摘要
目的:研究1个中国汉族早发型家族性阿尔茨海默病(EOFAD)家系的临床症状及其致病基因的突变形式。方法:收集1个EOFAD家系,分析2例患者及其他家系成员的临床表现及辅助检查结果。采集患者及部分家系成员外周血,提取基因组DNA,应用PCR联合直接测序法依次行早老素1(PS-1)基因、早老素2(PS-2)基因及淀粉样前体蛋白(APP)基因第16、17号外显子基因检测。结果:该家系2例患者发病年龄较早,均以记忆力下降为首发症状,病情呈进行性加重,均出现癫痫大发作及肌张力增高等其他痴呆类型少见的临床症状。在该家系2例患者中发现APP基因第17号外显子2 149位碱基发生G→A突变,使APP第717号氨基酸由缬氨酸变为异亮氨酸,发生V717I突变;未发现PS-1、PS-2基因突变。结论:在中国汉族EOFAD家系中发现了APP基因的V717I突变,进一步证明了APP基因突变是EOFAD的重要致病原因。
Aim： To analyze the clinical symptoms and mutation of pathogenic genes in a Chinese family with early-onset familial Alzheimer disease（ EOFAD）. Methods： The clinical features and the results of auxiliary examination were analyzed. By PCR and direct DNA sequencing,mutational analysis of presenilin-1（ PS-1）,presenilin-2（ PS-2）,and amyloid precursor protein（ APP） gene was performed. Results： The two patients with early onset age developed an insidious onset of difficulties in memory. They both showed epilepsy,hypermyotonia and some other symptoms which were rarely found in the course of the disease. Molecular genetic analysis revealed that the 2 patients had a mutation of c. 2 149 G→A in exon 17 of APP gene,which resulted in the amino acid substitution as V717 I. Conclusion： There is a V717 I mutation of the APP gene in a family with EOFAD,which demonstrates that APP gene mutation is the important pathogenesis of EOFAD.
出处
《郑州大学学报（医学版）》
CAS
北大核心
2015年第3期416-419,共4页
Journal of Zhengzhou University(Medical Sciences)
