Screening of the SETX gene in sporadic amyotrophic lateral sclerosis patients of Chinese origin

Abstract

Objective: To investigate all coding regions of amyotrophic lateral sclerosis (ALS)-related gene Senataxin (SETX) in sporadic amyotrophic lateral sclerosis patients of Chinese origin. Methods: From January 2010 to December 2014, the peripheral venous blood samples and clinical data were collected from 311 patients with sporadic amyotrophic lateral sclerosis (SALS) and 311 healthy controls who were of Chinese ancestry from the Department of Neurology, Chinese PLA General Hospital.Genomic DNA was extracted from peripheral venous blood of all participants using standard methods. The coding regions of SETX were amplified by polymerase chain reaction (PCR) and screened for mutations using next-generation sequencing technology. The online software SIFT and PolyPhen-2 were used to analyze the conservation of an altered amino acid and predict the potential pathogenicity of identified mutations. The SPSS 22.0 software was used to analyze the clinical feature of all participants. Results: Tenkinds of rare and one novel nonsynonymous mutations were identified and were absent in 311 controls. Twelve (3.86%) patients carried one SETX gene mutation. Five (1.61%) out of above-mentioned 12 patients carried highly pathogenic mutations including p. Pro1868Leu (c.5603G>A), p. Pro1331Leu (c.3992G>A), p. Glu756Val (c.2267T>A), p. Leu564Val (c.1690A>C), and p. Asn144Ser (c.431T>C). Patients carried SETX mutations were not different from other patients in onset age. Conclusion: Mutations in SETX are likely to be a pathogenesis for Chinese sporadic amyotrophic lateral sclerosis.