Background: Amyotrophic lateral sclerosis (ALS) is a complex neurological disorder characterized by rapid and progressive paralysis, eventually leading to respiratory failure. Approximately 10% of ALS cases are familial, stemming from specific genetic mutations that follow Mendelian inheritance patterns. Amyotrophic lateral sclerosis type 4 (ALS4) is a juvenile-onset form of familial ALS caused by mutations in the senataxin (SETX) gene. Advanced genomic technologies expedite the diagnosis of genetic disorders and enhance the quality of genetic support for patients and their families.
Methods: In this research, the detection of mutations in the SETX gene was performed through whole-exome sequencing (WES). The Polymerase Chain Reaction (PCR) technique was subsequently employed to validate the variant, followed by Sanger sequencing, and the resulting sequences were analyzed using Chromas Pro software.
Findings: The whole-exome sequencing results revealed a homozygous mutation in the gene (NM_015046:exon19:c.C6461T:p.T2154M) in the exome sequences of the affected offspring in the family.
Conclusion: This study highlights the advantage of utilizing WES for the genetic diagnosis of ALS. By investigating the genetic cause of ALS4, we can achieve a better understanding of the molecular biology of this disease.