Innovation Center for Neurological Disorders, Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.
Beijing Key Laboratory of Geriatric Cognitive Disorders, Beijing, China.
Mol Genet Genomic Med. 2020 Oct;8(10):e1443. doi: 10.1002/mgg3.1443. Epub 2020 Aug 6.
Mutations of three causative genes, namely presenilin 1 (PSEN1), presenilin 2 (PSEN2), and amyloid precursor protein (APP), have been identified as the major causes of early-onset familial Alzheimer's disease (EOFAD). The prevalence of causative gene mutations in patients with EOFAD has been reported in previous studies worldwide but remains unclear in China. The patients with these known mutations always show considerable clinical phenotypic variability. However, to date, there have been no detailed descriptions of the clinical phenotypes associated with these Chinese EOFAD mutations. Thus, the aim of this study was to describe all of the known mutations in three EOFAD causative genes and genotype-phenotype correlations in Chinese patients with EOFAD.
We systematically searched the PubMed, MEDLINE, CNKI, VIP, and WAN-FANG databases to find Chinese EOFAD mutations in reports from inception through May 2020.
We identified 31 studies reporting mutations of three causative genes in China. 10 mutations in APP gene, 27 mutations in PSEN1 gene and six mutations in PSEN2 were discovered in Chinese EOFAD. This review summarized all these probably pathogenic mutations as well as its clinical features. To the best of our knowledge, this is the first systemic review of causative gene mutations in patients with EOFAD in China.
The analysis of the genetic and clinical phenotype correlations in this review supports the idea that the clinical phenotype might be influenced by specific genetic defects. It also suggests genetic testing and genotype-phenotype correlations are important for the accurate diagnosis and for understanding disease-associated pathways and might also improve disease therapy and prevention.
早发性家族性阿尔茨海默病（EOFAD）的三个致病基因（早老素 1 基因（PSEN1）、早老素 2 基因（PSEN2）和淀粉样前体蛋白基因（APP））的突变已被确定为主要原因。先前的全球研究报告了 EOFAD 患者中致病基因突变的患病率，但在中国仍不清楚。具有这些已知突变的患者总是表现出相当大的临床表型变异性。然而，迄今为止，尚无关于这些中国 EOFAD 突变相关临床表型的详细描述。因此，本研究旨在描述 EOFAD 三种致病基因中所有已知突变以及与中国 EOFAD 患者相关的基因型-表型相关性。
我们系统地检索了 PubMed、MEDLINE、CNKI、VIP 和 WAN-FANG 数据库，以查找截至 2020 年 5 月发表的中国 EOFAD 报告中的突变。
我们确定了 31 项研究报告了中国三个致病基因的突变。在中国人 EOFAD 中发现了 APP 基因中的 10 个突变、PSEN1 基因中的 27 个突变和 PSEN2 基因中的 6 个突变。本综述总结了所有这些可能的致病性突变及其临床特征。据我们所知，这是对中国 EOFAD 患者致病基因突变的首次系统综述。
本综述中遗传和临床表型相关性的分析支持这样一种观点，即临床表型可能受到特定遗传缺陷的影响。它还表明基因检测和基因型-表型相关性对于准确诊断以及了解疾病相关途径非常重要，并且可能改善疾病治疗和预防。
