Early-onset Alzheimer disease caused by a new mutation (V717L) in the amyloid precursor protein gene
Early-onset Alzheimer disease caused by a new mutation (V717L) in the amyloid precursor protein gene
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DOI：
10.1001/archneur.57.6.885
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发表时间：
2000-06-01
影响因子：
--
通讯作者：
Ghetti, B
中科院分区：
文献类型：
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作者：
Murrell, JR;Hake, AM;Ghetti, B
背景：阿尔茨海默病是痴呆症的常见形式。在早发性阿尔茨海默病家族中发现了淀粉样前体蛋白 (APP)、早老素 1 (PS1) 和早老素 2 (PS2) 基因的突变。目的：确定早发性疾病家庭中痴呆的原因。设计、获取和参与者：有痴呆病史的家庭被转诊至印第安纳波利斯的印第安纳阿尔茨海默病中心。本研究中的所有研究都是在大学或大学医院进行的。先证者和她的 4 个兄弟姐妹参加了这项研究。该先证者仍然活着，在 38 岁时出现了阿尔茨海默病的症状。从 5 个家庭成员的血液样本中获得基因组 DNA。通过扩增和直接测序来筛选先证者的APP和PS1基因是否存在突变。结果：APP基因的外显子17的序列显示1个等位基因中存在单核苷酸（鸟嘌呤至胞嘧啶）取代，导致密码子717处的氨基酸变化（缬氨酸至亮氨酸）。通过直接测序对先证者的每个兄弟姐妹进行了这种突变检测。 4 人中的 2 人被发现有突变；其中一名患者最近在 36 岁时被临床诊断。结论：在一个有 30 多岁中后期开始痴呆病史的家族中发现了 APP 基因（V717L）的新突变。该家族的发病年龄比大多数其他也有 APP 突变的阿尔茨海默病家族要早。
Context: Alzheimer disease is the must common form of dementia. Mutations in the genes amyloid precursor protein (APP), presenilin 1 (PS1) and presenilin 2 (PS2) have been found in early-onset familial forms of Alzheimer disease.Objective: To determine the cause of dementia in a family with early-onset illness.Design, getting, and Participants: A family with a history of dementia was referred to the Indiana Alzheimer disease center, Indianapolis. All the research in this study was done in a university or university hospital. The proband and her 4 siblings took part in the study. The proband, who is still alive, showed symptoms of Alzheimer disease at 38 years of age. Genomic DNA was obtained from blood samples of 5 family members. The APP and PS1 genes of the proband were screened for mutations by amplification followed by direct sequencing.Results: Sequence of exon 17 of the APP gene revealed a single nucleotide (guanine to cytosine) substitution in 1 allele, resulting in an amino acid change at codon 717 (valine to leucine). Each of the proband's siblings were tested for this mutation by direct sequencing. Two of the 4 were found to have the mutation; one of whom was recently clinically diagnosed at the age of 36 years.Conclusions: A novel mutation in the APP gene (V717L) has been found in a family with a history of dementia, beginning in the mid to late 30s. The age of onset in this family is earlier than most of the other families with Alzheimer disease who also have APP mutations.