Department of Neurology, University of Thessaly, University Hospital of Larissa, Larissa, Greece.
Department of Hygiene and Epidemiology, Faculty of Medicine, University of Thessaly, Larissa, Greece.
Neurobiol Aging. 2019 Dec;84:238.e25-238.e34. doi: 10.1016/j.neurobiolaging.2019.04.012. Epub 2019 Apr 24.
A pathologic expansion of a noncoding GGGGCC hexanucleotide repeat of the C9orf72 gene has been strongly associated with familial amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD) cases predominantly in Caucasian populations. In the last decade, scientific interest had been drawn to this gene and many studies conducted have shown a possible correlation with other neurodegenerative diseases as well. We performed an extensive literature search for C9orf72 mutation and its frequency in various neurological and psychiatric diseases. In addition, we performed a meta-analysis of the data related to ALS and familial ALS. An online cloud-based database and an interactive map were developed. The overall mutation frequency of C9orf72 is 20% for familial FTD, 16% for familial ALS and around 6%-8% for sporadic ALS and FTD. The updated meta-analysis that we performed showed that the pooled frequency of C9orf72 repeat expansion in patients with familial ALS was 23% (CI: 18%-28%) and in patients with sporadic ALS 3% (CI: 3%-4%). The subgroup analysis regarding the origin of the population revealed significant differences between Caucasian and Asian patients. Our analysis supports the direct causal relation of the C9orf72 expansion in ALS and FTD. On the contrary, the role of C9orf72 in other neurodegenerative disorders remains controversial. The system that we developed-the online database and the interactive map-is hopefully a stepping stone for an ever-growing platform that will aid scientists from all over the world in contributing to the meta-analysis of C9orf72-related publications.
C9orf72 基因的非编码 GGGGCC 六核苷酸重复序列病理性扩张与家族性肌萎缩侧索硬化症（ALS）和额颞叶变性（FTD）病例密切相关，这些病例主要发生在白种人群中。在过去的十年中，科学界对该基因产生了浓厚的兴趣，许多研究表明它可能与其他神经退行性疾病也存在关联。我们对 C9orf72 突变及其在各种神经和精神疾病中的频率进行了广泛的文献检索。此外，我们还对与 ALS 和家族性 ALS 相关的数据进行了荟萃分析。开发了一个在线云数据库和一个交互式地图。C9orf72 的总体突变频率为：家族性 FTD 为 20%，家族性 ALS 为 16%，散发性 ALS 和 FTD 约为 6%-8%。我们进行的更新荟萃分析表明，家族性 ALS 患者中 C9orf72 重复扩增的合并频率为 23%（置信区间：18%-28%），散发性 ALS 患者为 3%（置信区间：3%-4%）。关于人群来源的亚组分析显示，白种人和亚洲患者之间存在显著差异。我们的分析支持 C9orf72 扩展在 ALS 和 FTD 中的直接因果关系。相反，C9orf72 在其他神经退行性疾病中的作用仍存在争议。我们开发的系统——在线数据库和交互式地图——有望成为一个不断发展的平台的基石，该平台将帮助来自世界各地的科学家为 C9orf72 相关出版物的荟萃分析做出贡献。
