Identification and functional analysis of novel mutations in the SOD1 gene in Chinese patients with amyotrophic lateral sclerosis

Abstract

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by selective involvement of motor neurons in the central nervous system (CNS). The most common causative gene of ALS in the Chinese population is the Cu/Zn superoxide dismutase 1 (SOD1) gene, which accounts for 20–42.9% of familial ALS (FALS) and 1–2% of sporadic ALS (SALS) cases. In this study, we identify three novel SOD1 mutations, Gly17Cys, Pro75Ser, and His121Gln, in four ALS pedigrees. A functional analysis was performed, and the results showed that all three mutations could lead to the formation of misfolded proteins. In addition, genotype–phenotype correlations in these patients are also described. Our study helps to characterize the genotype and phenotype of ALS with SOD1 mutations.

Keywords:

• Amyotrophic lateral sclerosis
• SOD1
• Chinese
• misfolded protein

Acknowledgements

The authors would like to thank all participants for their support and willingness to participate in this study.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Additional information

Funding

This work was supported by the grants [81671245, 81125009] to Zhi-Ying Wu from the National Natural Science Foundation of China and the Research Foundation for Distinguished Scholar of Zhejiang University to Zhi-Ying Wu [188020-193810101/089, Hangzhou].