Mutation analysis of SOD1, C9orf72, TARDBP and FUS genes in ethnically-diverse Malaysian patients with amyotrophic lateral sclerosis (ALS)

Neurobiol Aging. 2021 Dec:108:200-206. doi: 10.1016/j.neurobiolaging.2021.07.008. Epub 2021 Jul 21.

Abstract

Recent studies have identified SOD1, FUS, TARDBP and C9orf72 as major ALS-related genes in both European and Asian populations. However, significant differences exist in the mutation frequencies of these genes between various ancestral backgrounds. This study aims to identify the frequency of mutations in the common causative ALS genes in a multi-ethnic Malaysian cohort. We screened 101 Malaysian ALS patients including 3 familial and 98 sporadic cases for mutations in the coding regions of SOD1, FUS, and TARDBP by Sanger sequencing. The C9orf72 hexanucleotide repeat expansion was screened using the repeat-primed polymerase chain reaction assay. Mutations were found in 5.9% (6 of 101) of patients including 3.0% (3 of 101) of patients with the previously reported SOD1 missense mutations (p.V48A and p.N87S) and 3.0% (3 of 101) of patients with the C9orf72 repeat expansion. No mutations were found in the FUS and TARDBP genes. This study is the first to report the mutation frequency in an ethnically diverse Malaysian ALS population and warrants further investigation to reveal novel genes and disease pathways.

Keywords: Amyotrophic lateral sclerosis; C9orf72; FUS; Malaysia; SOD1; TARDBP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amyotrophic Lateral Sclerosis / ethnology*
  • Amyotrophic Lateral Sclerosis / genetics*
  • C9orf72 Protein / genetics*
  • Cohort Studies
  • DNA Mutational Analysis / methods
  • DNA Repeat Expansion / genetics
  • DNA-Binding Proteins / genetics*
  • Female
  • Genetic Association Studies*
  • Humans
  • Malaysia / ethnology
  • Male
  • Middle Aged
  • Mutation*
  • RNA-Binding Protein FUS / genetics*
  • Superoxide Dismutase-1 / genetics*

Substances

  • C9orf72 Protein
  • C9orf72 protein, human
  • DNA-Binding Proteins
  • FUS protein, human
  • RNA-Binding Protein FUS
  • SOD1 protein, human
  • TARDBP protein, human
  • Superoxide Dismutase-1