墨西哥肌萎缩侧索硬化患者中SOD1基因变异的鉴定

文献信息

中文摘要

肌萎缩侧索硬化（ALS）是一种快速进展、致命的神经退行性疾病，选择性累及运动神经元。临床表现包括进行性肌无力、肌萎缩、肌束颤动、吞咽困难和致命的呼吸衰竭。症状出现后的中位生存期通常为2至5年。尽管病情严重，拉丁美洲人群尤其是墨西哥人群中ALS的流行病学特征和遗传学图景仍不清楚。在本研究中，我们评估了一个由156例ALS患者组成的墨西哥队列中SOD1基因的突变谱。采用高分辨率熔解（HRM）分析和Sanger测序，我们在156例患者中的42例中鉴定出22个SOD1变异（总体变异携带频率为26.92%）。在21例患者中发现了致病性或可能致病性（P/LP）变异（13.5%）。值得注意的是，22个变异中有5个为新变异，扩展了SOD1变异的谱系。本研究中鉴定的变异携带频率高于欧洲人群报道的频率，但与亚洲人群观察到的频率相似。我们的结果凸显了墨西哥ALS独特的遗传异质性，并证明HRM是鉴定SOD1基因变异的一种快速有效的方法。

英文摘要

Amyotrophic Lateral Sclerosis (ALS) is a rapidly progressing, fatal neurodegenerative disorder that selectively affects motor neurons. Clinical manifestations include progressive muscle weakness, amyotrophy, fasciculations, dysphagia, and fatal respiratory failure. The median survival after symptom onset is typically 2 to 5 years. Despite its severity, the epidemiological profile and genetic landscape of ALS in Latin American populations, particularly in Mexico, remain unclear. In this study, we evaluated the mutational spectrum of the SOD1 gene in a Mexican cohort of 156 ALS patients. Using high-resolution melting (HRM) analysis and Sanger sequencing, we identified 22 SOD1 variants in 42 of 156 patients (overall variant carrier frequency, 26.92%). Pathogenic or likely pathogenic (P/LP) variants were found in 21 patients (13.5%). Notably, 5 of the 22 variants were novel, expanding the spectrum of SOD1 variants. The variant carrier frequency identified in this study is higher than that reported for European populations but similar to frequencies observed in Asian populations. Our results highlight the distinct genetic heterogeneity of ALS in Mexico and demonstrate that HRM is a rapid and effective method for identifying SOD1 gene variants.