具有路易体痴呆样临床表现的早老素-1基因突变家族性阿尔茨海默病一家系  

Familial Alzheimer＇s disease with presenilin 1 gene mutation presenting as dementia with Lewy bodies

作　　者：李珺[1] 贾树红[2] 乔亚男[2] 王康[2] 顾卫红[2] 钱端[1] 焦劲松[2] 金森[2] 

机构地区：[1]中日友好医院干部医疗科,北京100029 [2]中日友好医院干部神经内科

出　　处：《中华神经科杂志》2016年第1期40-44,共5页Chinese Journal of Neurology

摘　　要：目的研究1个有路易体痴呆样表现的早老素－1基因突变阿尔茨海默病家系的临床表现及存在的基因突变。方法分析该家系中患者的临床表现及辅助检查结果，采集先证者及其女儿的血样，并选100名健康体检者设立健康对照，提取基因组DNA，采用直接测序法进行早老素－1、微管相关蛋白tau（MAPT）基因检测。结果该家系中有3名成员具有路易体痴呆样临床表现，先证者及其女儿的早老素－1基因第12号外显子第1292位碱基均发生变异（C→T），导致第431位密码子编码的氨基酸由Ala变为Val。MAPT基因未发现致病突变。健康对照组未发现相似的早老素－1基因突变。结论该家系早老素－1基因发生A431V突变，证实在中国人群存在这一突变现象并且导致发病。该基因变异导致的家族性阿尔茨海默病也可以出现路易体痴呆样的特殊临床表现。Objective To analyze the phenotype and genetics in a Chinese pedigree with clinical manifestation of dementia with Lewy bodies （ DLB ）. Methods The clinical manifestations and auxiliary examination results were analyzed for the proband who had a dementia family history and his daughter. Peripheral blood of the proband, his daughter and 100 normal Chinese individuals was collected, and genomic DNA was extracted. PCR-sequencing of presenilin 1 （ PSEN1 ） and mierotubule-associated protein tau （MAPT） genes was performed. Results Three members of this family had the clinical manifestations of fluctuating cognitive impairment, parkinsonian symptoms and vivid visual hallucination, presenting as DLB. Sequencing results revealed that the proband and his daughter were heterozygous for a mutation 1 292 in exon 12 of PSEN1, causing the amino acid substitution Ala431Val. MAPT gene mutation was not found. No similar PSEN1 gene mutation was found in the normal control individuals examined. Conclusions We identified a mutation Ala431Val in the PSENI gene in Chinese patients. Familial Alzheimer＇s disease caused by PSEN1 mutation can present as DLB.

关 键 词：阿尔茨海默病 遗传现象 早老素1 路易体 系谱 

分 类 号：R749.16[医药卫生—神经病学与精神病学]