Since the discovery of the C9ORF72 gene in 2011, great advances have been achieved in its genetics and in identifying its role in disease models and pathological mechanisms; it is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). ALS patients with C9ORF72 expansion show heterogeneous symptoms. Those who are C9ORF72 expansion carriers have shorter survival after disease onset than non-C9ORF72 expansion patients. Pathological and clinical features of C9ORF72 patients have been well mimicked via several models, including induced pluripotent stem cell-derived neurons and transgenic mice that were embedded with bacterial artificial chromosome construct and that overexpressing dipeptide repeat proteins. The mechanisms implicated in C9ORF72 pathology include DNA damage, changes of RNA metabolism, alteration of phase separation, and impairment of nucleocytoplasmic transport, which may underlie C9ORF72 expansion-related ALS/FTD and provide insight into non-C9ORF72 expansion-related ALS, FTD, and other neurodegenerative diseases.

中文翻译：

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C9ORF72 基因在肌萎缩侧索硬化和额颞叶痴呆发病机制中的作用。

自2011 年发现C9ORF72基因以来，在其遗传学和确定其在疾病模型和病理机制中的作用方面取得了很大进展；它是肌萎缩侧索硬化 (ALS) 和额颞叶痴呆 (FTD) 的最常见遗传原因。具有C9ORF72扩增的ALS 患者表现出异质性症状。与非C9ORF72扩增患者相比，C9ORF72扩增携带者在发病后的生存期较短。病理和临床特征C9ORF72患者得到了很好的模仿通过几种模型，包括诱导多能干细胞衍生的神经元和嵌入细菌人工染色体构建体并过度表达二肽重复蛋白的转基因小鼠。C9ORF72病理学涉及的机制包括 DNA 损伤、RNA 代谢的变化、相分离的改变和核细胞质运输的损伤，这可能是C9ORF72扩增相关的 ALS/FTD 的基础，并提供对非C9ORF72扩增相关的 ALS、FTD、和其他神经退行性疾病。