摘要
目的 探讨1例儿童时期以癫痫起病的早发型阿尔茨海默病患者及其大家系的早老素基因1（PSEN1）突变情况。方法 选择2014年11月28日至2015年11月14日在北京大学第一医院神经内科门诊确诊为早发型阿尔茨海默病患者（先证者）及其大家系（ⅠⅣ代）为研究对象。本例先证者为男性,现年36岁,因“癫痫,异常家族史”就诊,于本院进行遗传咨询,希望明确病因。早发型阿尔茨海默病诊断标准：①发病年龄〈65岁;②临床检查结果支持痴呆的证据;③超过2个领域存在认知障碍;④进行性记忆力下降伴其他认知障碍;⑤无意识障碍;⑥无其他系统性疾病或脑疾病可解释的记忆和认知障碍。收集先证者及其家系成员临床资料,采用靶向捕获二代测序（TGS）技术对其进行基因分析,发现PSEN1突变后,对所有外显子和内含子边界PSEN1进行聚合酶链反应（PCR）检测,采用Sanger方法进行基因突变验证。本研究遵循的程序符合北京大学第一医院人体试验委员会所制定的伦理学标准,得到该委员会批准,并与受试者签署临床研究知情同意书。结果 ①本例先证者（Ⅲ16）于12岁时出现癫痫发作,15岁开始口服丙戊酸钠治疗后癫痫发作被控制,33岁停药后复发,再次采取丙戊酸钠缓释片治疗后癫痫被控制。本例先证者在本院进行相关检查的结果显示,智力、运动功能发育正常,头颅MRI检查结果未见异常,最终临床诊断为“原发性癫痫”。但是,患者自述于35岁开始出现记忆力下降,定向功能减退。②先证者的祖母（Ⅰ2）于30多岁出现精神障碍,40岁左右死亡。先证者的父亲（Ⅱ6）、2位伯父（Ⅱ2与Ⅱ3）、2位姑姑（Ⅱ4与Ⅱ5）均于35岁左右出现进行性记忆力下降、智能倒退,均于40岁左右死亡,并符合早发型阿尔茨海默病诊断标准,而被诊断为早发型阿尔茨海默病患者。③TGS检测结果显示,先证者PSEN1基
Objective To investigate the etiology of early-onset Alzheimer disease which caused by presenilin 1 （PSEN1） mutation in one case of early-onset Alzheimer disease patient with initial symptom of epilepsy childhood and his large family. Methods From November 28, 2014 to November 14, 2015, one case of patient with initial symptom of epilepsy from age of 12 years old who was diagnosed as early-onset Alzheimer disease （the proband） in Department of Neurology of Peking University First Hospital and his large family genealogy （Ⅰ -Ⅳ generations）were recruited as research objects. Diagnostic criteria of Alzheimer disease were as follows. （1）Age of onset less than 65 years old. （2）The clinical examination evidence supported the diagnosis for dementia; （3）Cognitive impairment showed in more than two fields. （4）The progressive decline of memory and with other cognitive disorders. （5）Without disturbance of consciousness.（6）Without other systemic diseases and the memory and cognitive impairment which can be explained by the brain diseases. The proband, a male, 36 years old had seizures from the age of 12-year-old. He visited the hospital to seek for etiological and to study for his abnormal family history. Clinical data and genomic DNA of the proband and his family members were collected. Targeted next-generation sequencing （TGS） was performed to detect the PSEN1 mutation in the proband. All exons and exon-intron boundaries of PSEN1 were checked by polymerase chain reaction （PCR）. Sanger sequencing was used to verify the corresponding mutation. The procedure of this study was consistent with ethical standard established by the committee of investigation in human beings of Peking University First Hospital. And it was approved by this committee. Informed consent was obtained from all participants. Results （1）The proband （ Ⅲ 16 ） presented with seizures when he was 12 years old. After treated by sodium valproate from the age of 15 years old, the seizure was not observed. H
出处
《中华妇幼临床医学杂志（电子版）》
CAS
2016年第6期621-626,共6页
Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition)
基金
"十二五"国家科技支撑计划项目(2012BAI09B04)
北京市重点实验室儿科遗传性疾病分子诊断与研究基金项目(Z141107004414036)~~
