对非裔美国人早发性阿尔茨海默病基因中的疾病风险变异进行综合筛查，发现了新的PSEN变异。
Comprehensive Screening for Disease Risk Variants in Early-Onset Alzheimer's Disease Genes in African Americans Identifies Novel PSEN Variants.
作者信息
N'Songo Aurelie, Carrasquillo Minerva M, Wang Xue, Nguyen Thuy, Asmann Yan, Younkin Steven G, Allen Mariet, Duara Ranjan, Custo Maria T Greig, Graff-Radford Neill, Ertekin-Taner Nilüfer
机构信息
Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Department of Health Science Research, Mayo Clinic, Jacksonville, FL, USA.
出版信息
J Alzheimers Dis. 2017;56(4):1215-1222. doi: 10.3233/JAD-161185.
Abstract
We conducted a comprehensive screening of rare coding variants in an African American cohort to identify novel pathogenic mutations within the early-onset Alzheimer's disease (EOAD) genes (APP, PSEN1, and PSEN2) in this understudied population. Whole-exome sequencing of 238 African American subjects identified 6 rare missense variants within the EOAD genes, which were observed in AD cases but never among controls. These variants were analyzed in an independent cohort of 300 African American subjects in which PSEN2:NM_000447:exon5:c.T331C:p.Phe111Leu and PSEN1-minilin rs777923890 variants were again not observed, indicating that these novel rare variants, may contribute to AD risk in this population.
摘要
我们对一个非裔美国人队列进行了罕见编码变异的全面筛查，以在这个研究较少的人群中确定早发性阿尔茨海默病（EOAD）基因（APP、PSEN1和PSEN2）内的新型致病突变。对238名非裔美国人受试者进行全外显子组测序，在EOAD基因中鉴定出6个罕见错义变异，这些变异在AD病例中观察到，但在对照中从未出现过。在一个由300名非裔美国人组成的独立队列中对这些变异进行了分析，其中再次未观察到PSEN2:NM_000447:exon5:c.T331C:p.Phe111Leu和PSEN1-小菌素rs777923890变异，表明这些新型罕见变异可能导致该人群患AD的风险。
相似文献
1
Comprehensive Screening for Disease Risk Variants in Early-Onset Alzheimer's Disease Genes in African Americans Identifies Novel PSEN Variants.对非裔美国人早发性阿尔茨海默病基因中的疾病风险变异进行综合筛查，发现了新的PSEN变异。
J Alzheimers Dis. 2017;56(4):1215-1222. doi: 10.3233/JAD-161185.
2
, and Mutations in Asian Patients with Early-Onset Alzheimer Disease.携带 PSEN1、PSEN2 和 APP 突变的早发性阿尔茨海默病亚洲患者。
Int J Mol Sci. 2019 Sep 25;20(19):4757. doi: 10.3390/ijms20194757.
3
Exome sequencing identifies 2 novel presenilin 1 mutations (p.L166V and p.S230R) in British early-onset Alzheimer's disease.外显子组测序在英国早发性阿尔茨海默病中鉴定出2种新的早老素1突变（p.L166V和p.S230R）。
Neurobiol Aging. 2014 Oct;35(10):2422.e13-6. doi: 10.1016/j.neurobiolaging.2014.04.026. Epub 2014 May 2.
4
Association of Early-Onset Alzheimer Disease With Elevated Low-Density Lipoprotein Cholesterol Levels and Rare Genetic Coding Variants of APOB.早发性阿尔茨海默病与低密度脂蛋白胆固醇水平升高及 APOB 罕见遗传编码变异的关联。
JAMA Neurol. 2019 Jul 1;76(7):809-817. doi: 10.1001/jamaneurol.2019.0648.
5
Genetic screening in early-onset Alzheimer's disease identified three novel presenilin mutations.早发性阿尔茨海默病的基因筛查发现了三种新型早老素突变。
Neurobiol Aging. 2020 Feb;86:201.e9-201.e14. doi: 10.1016/j.neurobiolaging.2019.01.015. Epub 2019 Jan 29.
6
Screening for Genetic Mutations Associated with Early-Onset Alzheimer's Disease in Han Chinese.汉族人群早发性阿尔茨海默病相关基因突变的筛查
Curr Alzheimer Res. 2022;19(10):724-733. doi: 10.2174/1567205020666221028112915.
7
Rare variants in APP, PSEN1 and PSEN2 increase risk for AD in late-onset Alzheimer's disease families.载脂蛋白 APP、早老素 1 和早老素 2 的罕见变异可增加晚发性阿尔茨海默病家族性阿尔茨海默病的风险。
PLoS One. 2012;7(2):e31039. doi: 10.1371/journal.pone.0031039. Epub 2012 Feb 1.
8
Causative Mutations and Genetic Risk Factors in Sporadic Early Onset Alzheimer's Disease Before 51 Years.51 岁前散发型早发性阿尔茨海默病的致病突变和遗传风险因素
J Alzheimers Dis. 2019;71(1):227-243. doi: 10.3233/JAD-190193.
9
Mutation screening in Chinese patients with familial Alzheimer's disease by whole-exome sequencing.通过全外显子组测序对中国家族性阿尔茨海默病患者进行突变筛查。
Neurobiol Aging. 2019 Apr;76:215.e15-215.e21. doi: 10.1016/j.neurobiolaging.2018.11.024. Epub 2018 Dec 6.
10
Investigating the role of rare coding variability in Mendelian dementia genes (APP, PSEN1, PSEN2, GRN, MAPT, and PRNP) in late-onset Alzheimer's disease.研究罕见编码变异在晚发性阿尔茨海默病中孟德尔痴呆基因（APP、PSEN1、PSEN2、GRN、MAPT和PRNP）中的作用。
Neurobiol Aging. 2014 Dec;35(12):2881.e1-2881.e6. doi: 10.1016/j.neurobiolaging.2014.06.002. Epub 2014 Jun 16.
引用本文的文献
1
Clinical Significance of Early-Onset Alzheimer's Mutations in Asian and Western Populations: A Scoping Review.亚洲和西方人群早发性阿尔茨海默病突变的临床意义：一项范围综述
Genes (Basel). 2025 Mar 17;16(3):345. doi: 10.3390/genes16030345.
2
Genetics of Alzheimer's Disease in the African American Population.非裔美国人中阿尔茨海默病的遗传学
J Clin Med. 2023 Aug 9;12(16):5189. doi: 10.3390/jcm12165189.
3
Association of Plasma Biomarkers of Alzheimer Disease With Cognition and Medical Comorbidities in a Biracial Cohort.阿尔茨海默病血浆生物标志物与一个多种族队列认知功能和合并症的相关性。
Neurology. 2023 Oct 3;101(14):e1402-e1411. doi: 10.1212/WNL.0000000000207675. Epub 2023 Aug 14.
4
Plasma Biomarkers of Alzheimer's Disease in African Americans.非裔美国人阿尔茨海默病的血浆生物标志物。
J Alzheimers Dis. 2021;79(1):323-334. doi: 10.3233/JAD-200828.
5
Genetic variation in neurodegenerative diseases and its accessibility in the model organism Caenorhabditis elegans.神经退行性疾病中的遗传变异及其在模式生物秀丽隐杆线虫中的可及性。
Hum Genomics. 2017 May 25;11(1):12. doi: 10.1186/s40246-017-0108-4.
本文引用的文献
1
Analysis of protein-coding genetic variation in 60,706 humans.对60706名人类的蛋白质编码基因变异进行分析。
Nature. 2016 Aug 18;536(7616):285-91. doi: 10.1038/nature19057.
2
Genomic variant annotation and prioritization with ANNOVAR and wANNOVAR.使用ANNOVAR和wANNOVAR进行基因组变异注释和优先级排序。
Nat Protoc. 2015 Oct;10(10):1556-66. doi: 10.1038/nprot.2015.105. Epub 2015 Sep 17.
3
Whole-Exome Enrichment with the Agilent SureSelect Human All Exon Platform.使用安捷伦SureSelect人类全外显子平台进行全外显子富集。
Cold Spring Harb Protoc. 2015 Mar 11;2015(7):626-33. doi: 10.1101/pdb.prot083659.
4
Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.序列变异解读的标准与指南：美国医学遗传学与基因组学学会和分子病理学协会的联合共识推荐
Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.
5
Rarity of the Alzheimer disease-protective APP A673T variant in the United States.美国阿尔茨海默病保护性APP A673T变体的罕见性。
JAMA Neurol. 2015 Feb;72(2):209-16. doi: 10.1001/jamaneurol.2014.2157.
6
Investigating the role of rare coding variability in Mendelian dementia genes (APP, PSEN1, PSEN2, GRN, MAPT, and PRNP) in late-onset Alzheimer's disease.研究罕见编码变异在晚发性阿尔茨海默病中孟德尔痴呆基因（APP、PSEN1、PSEN2、GRN、MAPT和PRNP）中的作用。
Neurobiol Aging. 2014 Dec;35(12):2881.e1-2881.e6. doi: 10.1016/j.neurobiolaging.2014.06.002. Epub 2014 Jun 16.
7
Investigation of an amyloid precursor protein protective mutation (A673T) in a North American case-control sample of late-onset Alzheimer's disease.北美晚发性阿尔茨海默病病例对照样本中淀粉样前体蛋白保护性突变（A673T）的研究。
Neurobiol Aging. 2014 Jul;35(7):1779.e15-6. doi: 10.1016/j.neurobiolaging.2014.01.020. Epub 2014 Jan 23.
8
A general framework for estimating the relative pathogenicity of human genetic variants.一种用于估计人类遗传变异相对致病性的通用框架。
Nat Genet. 2014 Mar;46(3):310-5. doi: 10.1038/ng.2892. Epub 2014 Feb 2.
9
A novel PSEN1 mutation (I238M) associated with early-onset Alzheimer's disease in an African-American woman.一名非裔美国女性中与早发性阿尔茨海默病相关的新型PSEN1突变（I238M）。
J Alzheimers Dis. 2014;40(2):271-5. doi: 10.3233/JAD-131844.
10
Alzheimer's disease: analyzing the missing heritability.阿尔茨海默病：分析缺失的遗传性。
PLoS One. 2013 Nov 7;8(11):e79771. doi: 10.1371/journal.pone.0079771. eCollection 2013.
Zotero 插件