Instituto de Medicina Molecular and Institute of Physiology, Faculdade de Medicina, Universidade de Lisboa, Avenida Professor Egas Moniz, Lisbon, Portugal.
Instituto de Medicina Molecular and Institute of Physiology, Faculdade de Medicina, Universidade de Lisboa, Avenida Professor Egas Moniz, Lisbon, Portugal; Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.
Neurobiol Aging. 2018 Oct;70:325.e7-325.e15. doi: 10.1016/j.neurobiolaging.2018.05.009. Epub 2018 May 14.
Mutation frequency of the 2 main amyotrophic lateral sclerosis (ALS)-related genes, C9orf72 and SOD1, varies considerably across the world. We analyzed those genes in a large population of Portuguese ALS patients (n = 371) and recorded demographic and clinical features. Familial ALS (FALS) was disclosed in 11.6% of patients. Mutations in either SOD1 or C9orf72 were found in 9.2% of patients and accounted for 40% of FALS and 5.2% of sporadic ALS. SOD1 mutations were rare (0.83%), but a novel and probably disease-causing mutation was identified: p.Ala152Pro (c.457G>C). The C9orf72 hexanucleotide repeat expansion was the commonest abnormality, accounting for 4.6% of sporadic ALS and 37.5% of FALS; in these patients, Frontotemporal Dementia was prevalent. This first report on the frequency of C9orf72 hexanucleotide repeat expansion and SOD1 mutations in Portuguese ALS patients reiterate that the genetic architecture of ALS varies among different geographic regions. The mutations incidence in ALS patients (∼10%) and associated phenotypes suggest that genetic tests should be offered to more patients, and other genes should be investigated in our population.
2 种主要的肌萎缩侧索硬化症 (ALS) 相关基因，即 C9orf72 和 SOD1 的突变频率在全球范围内差异很大。我们分析了 371 名葡萄牙 ALS 患者的大样本中的这些基因，并记录了人口统计学和临床特征。11.6%的患者存在家族性 ALS (FALS)。在 9.2%的患者中发现了 SOD1 或 C9orf72 的突变，占 FALS 的 40%和散发性 ALS 的 5.2%。SOD1 突变非常罕见（0.83%），但发现了一种新的、可能导致疾病的突变：p.Ala152Pro (c.457G>C)。C9orf72 六核苷酸重复扩增是最常见的异常，占散发性 ALS 的 4.6%和 FALS 的 37.5%；在这些患者中，额颞叶痴呆很常见。这是首次在葡萄牙 ALS 患者中报告 C9orf72 六核苷酸重复扩增和 SOD1 突变的频率，再次表明 ALS 的遗传结构在不同地理区域存在差异。ALS 患者的突变发生率（约 10%）和相关表型表明，应向更多患者提供基因检测，并在我们的人群中调查其他基因。
