Next-generation sequencing reveals a novel pathogenic variant in the ATM gene

Int J Neurosci. 2022 Jun;132(6):558-562. doi: 10.1080/00207454.2020.1826944. Epub 2021 Jan 24.

Abstract

Introduction: Ataxia telangiectasia (A-T) is a rare autosomal recessive, multisystemic disease. Patients with the A-T syndrome present a broad spectrum of disease phenotypes. The ATM (ataxia telangiectasia mutated) gene, the only causative gene for A-T.

Method: A patient of Persian origin presenting with typical A-T was referred to our genetics centre for specialized genetic counselling and testing. Targeted next-generation sequencing (NGS) was applied. Sanger sequencing was used to confirm the candidate variant. Modelling was performed using the SWISS-MODEL server.

Results: A homozygous stop-gain variant c.829G > T (p.E277*) was found in the ATM gene. This variant was confirmed by Sanger sequencing and modelling of native structure, and truncated structure was performed.

Conclusion: To date, very few pathogenic variants of the ATM gene have been reported from the Iranian population. The finding has implications in molecular diagnostic for A-T in Iran.

Keywords: Ataxia telangiectasia; Iran; next-generation sequencing; the ATM gene.

MeSH terms

  • Ataxia Telangiectasia Mutated Proteins / genetics
  • Ataxia Telangiectasia* / genetics
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Iran
  • Mutation / genetics
  • Phenotype

Substances

  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins