Molecular diagnosis of autosomal dominant early onset Alzheimer's disease:: an update
Molecular diagnosis of autosomal dominant early onset Alzheimer's disease:: an update
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DOI：
10.1136/jmg.2005.033456
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发表时间：
2005-10-01
影响因子：
4
通讯作者：
Campion, D
中科院分区：
文献类型：
--
作者：
Raux, G;Guyant-Maréchal, L;Campion, D
背景：常染色体显性遗传早发性阿尔茨海默病（ADEOAD）具有遗传异质性。目的：探讨淀粉样前体蛋白（APP）、早老素1（PSEN 1）和早老素2（PSEN 2）基因在ADEOAD发病中的作用。他们是使用严格的标准确定的（在三代人中，60岁之前发病的可能或确定的阿尔茨海默病病例的发生）。所有病例均符合NINCDS-ADRDA关于可能或确定的阿尔茨海默病的标准。结果：在31个家系中，有24个家系检测到PSEN 1基因突变，其中8个为未报道的突变; 5个家系检测到APP基因突变。在这个样本中，PSEN 1和APP突变携带者的平均发病年龄分别为41.7和51.2 years，either.Conclusions：将这些数据与以前发表的数据相结合，产生65个ADEOAD家族，66%的病例可归因于PSEN 1突变，16%归因于APP突变，而18%仍无法解释。
Background: Autosomal dominant early onset Alzheimer's disease (ADEOAD) is genetically heterogeneous. Mutations of the amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) genes have been identified.Objective: To further clarify the respective contribution of these genes to ADEOAD.Methods: 31 novel families were investigated. They were ascertained using stringent criteria ( the occurrence of probable or definite cases of Alzheimer's disease with onset before 60 years of age in three generations). All cases fulfilled the NINCDS-ADRDA criteria for probable or definite Alzheimer's disease. The entire coding regions of PSEN1 and PSEN2 genes and exons 16 and 17 of APP gene were sequenced from genomic DNAResults: PSEN1 mutations, including eight previously unreported mutations, were detected in 24 of the 31 families, and APP mutations were found in five families. In this sample, the mean ages of disease onset in PSEN1 and APP mutation carriers were 41.7 and 51.2 years, respectively.Conclusions: Combining these data with previously published data, yielding 65 ADEOAD families, 66% of the cases were attributable to PSEN1 mutations and 16% to APP mutations, while 18% remained unexplained.