Autosomal dominant early onset Alzheimer's disease in the Mexican state of Jalisco: High frequency of the mutation PSEN1 c.1292C>A and phenotypic profile of patients
Autosomal dominant early onset Alzheimer's disease in the Mexican state of Jalisco: High frequency of the mutation PSEN1 c.1292C>A and phenotypic profile of patients
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DOI：
10.1002/ajmg.c.31865
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发表时间：
2020-12-04
影响因子：
3.1
通讯作者：
Figuera, Luis E.
中科院分区：
文献类型：
--
作者：
Dumois-Petersen, Sofia;Gallegos-Arreola, Martha P.;Figuera, Luis E.
APP、PSEN1和PSEN2三个基因的突变是常染色体显性早发性阿尔茨海默病（AD-EOAD）的主要原因。在PSEN1中，A431E （c.1292C>A, rs63750083）突变被怀疑在墨西哥哈利斯科州产生了始创效应。在墨西哥哈利斯科州的瓜达拉哈拉，在评估AD-EOAD的46例指标病例中发现了该突变。在我们的家谱分析中，确定了301名突变携带者的受影响亲属，其中195人在访谈时已经死亡。此外，560名后代携带突变的风险为50%，348名后代有潜在风险。对39例患者进行了系统的表型分析。平均发病年龄为42.5±3.9岁，男女患者发病年龄无显著差异。此外，观察到大量的临床异质性和高频率的痉挛性截瘫、语言障碍和神经精神症状。据我们所知，被调查的家庭代表了拉丁美洲携带PSEN1突变的第二大人群，为研究阿尔茨海默病的遗传基础提供了独特的机会。解决AD-EOAD需要一个完整的方法，包括对其临床行为的深刻理解，以及咨询协议和预防研究。
Mutations in three genes (APP, PSEN1, and PSEN2) are the main cause of the autosomal dominant early-onset Alzheimer's disease (AD-EOAD). In PSEN1, the A431E (c.1292C>A, rs63750083) mutation is suspected to have exerted a founder effect in the State of Jalisco, Mexico. In Guadalajara, Jalisco, Mexico, this mutation was found in 46 index cases evaluated for AD-EOAD. In our genealogical analysis, 301 affected relatives of the mutation carriers were identified, 195 of whom were already deceased at the time of interview. Moreover, 560 descendants had a 50% risk of carrying the mutation, and 348 were potentially at risk. A systematic phenotyping was performed in 39 patients. The mean onset age was 42.5 +/- 3.9 years, and no significant difference in onset age was observed between the male and female patients. Furthermore, a substantial clinical heterogeneity and high frequencies of spastic paraparesis, language disorders, and neuropsychiatric symptoms were observed. To our knowledge, the investigated families represent the second biggest population carrying a PSEN1 mutation in Latin America, offering a unique opportunity to study the genetic basis of Alzheimer's disease. Addressing AD-EOAD warrants an integral approach involving a deep understanding of its clinical behavior, as well as counseling protocols and prevention studies.