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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

Feng Wang1, Shengyu Fu2, Jiafan Lei1, Hongchen Wu3, Shugui Shi3, Kangning Chen4, Jun Hu4, Xueqing Xu1
  • 1Department of Clinical Laboratory, Shenzhen Baoan Women's and Children's Hospital, Jinan University, Shenzhen, China
  • 2Faculty of Health Sciences, University of Macau, Taipa, Macau, China
  • 3Department of Neurology, Chunking General Hospital, Chongqing, China
  • 4Department of Neurology, First Affiliated Hospital of Army Medical University, Army Medical University, Chongqing, China
* Co-first authors
Received: May 9, 2020Accepted: July 30, 2020Published: November 5, 2020
https://doi.org/10.18632/aging.103967

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.

Abstract

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.