摘要
目的:报道4例经过脑脊液阿尔茨海默病(alzheimer's disease,AD)标志物和基因检测确诊的PS-1基因杂合突变的早发型AD患者临床表现和病情进展速度的差异。方法:4例早发型痴呆患者通过痴呆家族史调查、神经心理学评估、神经系统查体、头颅MRI、脑脊液AD标志物和全外显子测序检测。结果:此4例患者脑脊液AD标志物检测结果均符合ATN诊断框架,并且均经过基因全外显子测序确认为PS-1基因杂合突变,病例1为携带PS-1杂合突变位点(c.1186G>A),病例2和病例3携带PS-1基因同一杂合突变位点(c.791C>T),病例2同时携带额颞叶痴呆致病基因GRN基因杂合突变位点(c.329G>A),病例4携带PS-1基因杂合突变位点(c.265G>C),其中病例1、病例3和病例4均有痴呆家族史,病例2无痴呆家族史,病例2和病例3发病年龄相同,但是病例2的病情进展速度明显快于病例3,病例4的发病年龄为38岁,明显早于其家族其他成员痴呆发病年龄(50岁),病例4在儿童时期有脑震荡病史。结论:PS-1基因突变所致早发型AD并非皆有痴呆家族史,从头突变并不少见,不同PS-1基因突变位点导致AD发病年龄不同,同一PS-1基因杂合突变导致AD发病年龄相同,但是后天因素包括教育程度、工作的复杂程度和脑外伤等也会对PS-1基因突变所致早发型AD的临床表现和进展速度产生显著影响。
Objective:To report the differences in clinical manifestations and disease progression rate of 4 patients with early-onset Alzheimer's disease(AD)who were diagnosed with PS-1 gene heterozygous mutation by cerebrospinal fluid markers and gene detection.Methods:Four patients with early-onset dementia were examined by family history investigation,neuropsychological evaluation,physical examination of nervous system,MRI of head,AD markers in cerebrospinal fluid and whole exon sequencing.Results:The detection results of AD markers in cerebrospinal fluid of these four patients were all in line with the ATN diagnostic framework,and all of them were confirmed to be PS-1 heterozygous mutation by gene whole exon sequencing.Case 1 carried PS-1 heterozygous mutation site(c.1186G>A),and cases 2 and 3 carried the same heterozygous mutation site of PS-1 gene(c.791C>T).Case 2 carries the heterozygous mutation site of GRN gene(c.329G>A),and case 4 carries the heterozygous mutation site of PS-1 gene(c.265G>C),among which case 1,case 3 and case 4 all have family history of dementia,case 2 has no family history of dementia,and the onset age of case 2 and case 3 is the same,but the progress speed of case 2 is obviously faster than that of case 3.The onset age of case 4 was 38 years old,which was significantly earlier than that of other members of his family(50 years old).Case 4 had a history of concussion in childhood.Conclusion:Not all early-onset AD caused by PS-1 gene mutation have a family history of dementia,and de novo mutation is not uncommon.Different PS-1 gene mutation sites lead to different onset ages of AD,and the same PS-1 gene heterozygous mutation leads to the same onset age of AD.However,acquired factors including education level,complexity of work and brain trauma will also have a significant impact on the clinical manifestations and progress rate of early-onset AD caused by PS-1 gene mutation.
作者
朱飞奇
许春燕
邱国真
郭启雯
陈淳淳
Feiqi ZHU;Chunyan XU;Guozhen QIU;Qiwen GUO;Chunchun CHEN(Cognitive Impairment Ward of Neurology Department,the Luohu People’s hospital,Shenzhen,Guangdong province,518001,China)
出处
《阿尔茨海默病及相关病杂志》
2023年第1期43-49,共7页
Chinese Journal of Alzheimer's Disease and Related Disorders
基金
深圳市医疗卫生三名工程项目“瑞典卡罗琳斯卡医学院NVS系Bengt Winblad教授阿尔茨海默病团队”(SZSM201801014)资助
深圳市科创委重点项目“AD前期及患者健康管理大数据构建及其预测预警模型研究”(JCYJ20200109143431341)资助。
