Genetic screening of Alzheimer's disease genes in Iberian and African samples yields novel mutations in presenilins and APP.
Genetic screening of Alzheimer's disease genes in Iberian and African samples yields novel mutations in presenilins and APP.
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DOI：
10.1016/j.neurobiolaging.2008.06.012
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发表时间：
2010-05
影响因子：
4.2
通讯作者：
Clarimon, Jordi
中科院分区：
文献类型：
--
作者：
Guerreiro, Rita Joao;Baquero, Miguel;Blesa, Rafael;Boada, Merce;Bras, Jose Miguel;Bullido, Maria J.;Calado, Ana;Crook, Richard;Ferreira, Carla;Frank, Ana;Gomez-Isla, Teresa;Hernandez, Isabel;Lleo, Alberto;Machado, Alvaro;Martinez-Lage, Pablo;Masdeu, Jose;Molina-Porcel, Laura;Molinuevo, Jose L.;Pastor, Pau;Perez-Tur, Jordi;Relvas, Rute;Oliveira, Catarina Resende;Ribeiro, Maria Helena;Rogaeva, Ekaterina;Sa, Alfredo;Samaranch, Lluis;Sanchez-Valle, Raquel;Santana, Isabel;Tarraga, Lluis;Valdivieso, Fernando;Singleton, Andrew;Hardy, John;Clarimon, Jordi
早发性（<65 岁）阿尔茨海默病 (AD) 患者中已发现三个基因（PSEN1、PSEN2 和 APP）突变。我们对来自伊比利亚半岛的 231 名临床诊断为早发 AD 的患者（平均发病年龄 52.9 岁；范围 31-64）进行了早老素编码区以及 APP 基因外显子 16 和 17 的突变筛查。我们发现 PSEN1 中的三个新突变、PSEN2 中的一个新突变以及 APP 基因中的一个新突变。还发现了四种先前描述的 PSEN1 突变。对来自伊比利亚半岛的 121 名老年健康对照者和属于人类多态性研究中心-人类基因组多样性小组 (CEPH-HGDP) 的 7 个非洲人群的 130 名个体进行了相同的分析，以确定这些基因的正常变异程度。有趣的是，在后一个系列中，我们在所有三个基因中发现了五个新的非同义变化，以及先前与 AD 相关的早老素 2 变体 (R62H)。在其中一些突变中，病理后果是不确定的，需要进一步研究。为了解决这个问题，我们提出并使用一种系统算法对 AD 突变的假定病理学进行分类。
Mutations in three genes (PSEN1, PSEN2, and APP) have been identified in patients with early-onset (<65years) Alzheimer’s disease (AD). We performed a screening for mutations in the coding regions of presenilins, as well as exons 16 and 17 of the APP gene in a total of 231 patients from the Iberian peninsular with a clinical diagnosis of early onset AD (mean age at onset of 52.9 years; range 31–64). We found three novel mutations in PSEN1, one novel mutation in PSEN2, and a novel mutation in the APP gene. Four previously described mutations in PSEN1 were also found. The same analysis was carried in 121 elderly healthy controls from the Iberian peninsular, and a set of 130 individuals from seven African populations belonging to the Centre d’Etude du Polymorphisme Humain-Human Genome Diversity Panel (CEPH-HGDP), in order to determine the extent of normal variability in these genes. Interestingly, in the latter series, we found five new nonsynonymous changes in all three genes and a presenilin 2 variant (R62H) that has been previously related to AD. In some of these mutations, the pathologic consequence is uncertain and needs further investigation. To address this question we propose and use a systematic algorithm to classify the putative pathology of AD mutations.
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影响因子：
2.5
作者：
Houlden, H;Crook, R;Hardy, J
通讯作者：
Hardy, J
影响因子：
4.4
作者：
Kametani, F;Tanaka, K;Mori, H
通讯作者：
Mori, H
影响因子：
4
作者：
Raux, G;Guyant-Maréchal, L;Campion, D
通讯作者：
Campion, D
影响因子：
11.2
作者：
Mattila, KM;Forsell, C;Lannfelt, L
通讯作者：
Lannfelt, L
影响因子：
11.2
作者：
Ikeda, M;Sharma, V;StGeorgeHyslop, PH
通讯作者：
StGeorgeHyslop, PH