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.

中文翻译：

---

墨西哥哈利斯科州常染色体显性早发性阿尔茨海默病：PSEN1 c.1292C>A 突变的高频率和患者的表型特征

三个基因（APP、PSEN1和PSEN2）的突变是常染色体显性遗传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发挥了创始效应。在墨西哥哈利斯科州的瓜达拉哈拉，在 46 个针对 AD-EOAD 评估的指标病例中发现了这种突变。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 人在采访时已经死亡。此外，560 名后代有 50% 的风险携带突变，348 名有潜在风险。对 39 名患者进行了系统的表型分析。平均发病年龄为 42.5 ± 3.9 岁，男性和女性患者的发病年龄无显着差异。此外，观察到大量临床异质性和高频率的痉挛性下肢轻瘫、语言障碍和神经精神症状。据我们所知，拉丁美洲的PSEN1突变，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，包括深入了解其临床行为，以及咨询方案和预防研究。