Research Paper Volume 12, Issue 22 pp 22859—22868
Identification of novel FUS and TARDBP gene mutations in Chinese amyotrophic lateral sclerosis patients with HRM analysis
- 1 Department of Clinical Laboratory, Shenzhen Baoan Women's and Children's Hospital, Jinan University, Shenzhen, China
- 2 Faculty of Health Sciences, University of Macau, Taipa, Macau, China
- 3 Department of Neurology, Chunking General Hospital, Chongqing, China
- 4 Department of Neurology, First Affiliated Hospital of Army Medical University, Army Medical University, Chongqing, China
Received: May 9, 2020 Accepted: July 30, 2020 Published: November 5, 2020https://doi.org/10.18632/aging.103967
How to Cite
Copyright: © 2020 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive loss of motor neurons. More than 30 genes have been linked to ALS to date, including FUS and TARDBP, which exhibit similar roles in RNA metabolism. This study explored the use of high-resolution melting (HRM) analysis to screen for FUS and TARDBP mutation hotspot regions in 146 Chinese ALS patients, which achieved 100% detection. Two FUS mutations were observed in two different familial ALS probands, a missense mutation (p.R521H) and a novel splicing mutation (c.1541+1G>A). Five TARDBP mutations were identified in six ALS patients, including a novel 3’UTR mutation (c.*731A>G) and four missense mutations (p.G294V, p.M337V, p.G348V, and p.I383V). We found that FUS mutations were present in 1.4% of Chinese ALS patients, whereas TARDBP mutations were responsible for 4.1% of Chinese ALS cases. Here, we describe the accuracy of using highly sensitive HRM analysis to identify two novel FUS and TARDBP mutations in Chinese sporadic and familial ALS cases. Our study contributes to the further understanding of the genetic and phenotypic diversity of ALS.