ATM mutation spectrum in Russian children with ataxia-telangiectasia

Eur J Med Genet. 2020 Jan;63(1):103630. doi: 10.1016/j.ejmg.2019.02.003. Epub 2019 Feb 14.


Ataxia-telangiectasia (AT) is a severe autosomal recessive orphan disease characterized by a number of peculiar clinical manifestations. Genetic diagnosis of AT is complicated due to a large size of the causative gene, ATM. We used next-generation sequencing (NGS) technology for the ATM analysis in 17 children with the clinical diagnosis of AT. Biallelic mutations in the ATM gene were identified in all studied subjects; these lesions included one large gene rearrangement, which was reliably detected by NGS and validated by multiplex ligation-dependent probe amplification (MLPA). There was a pronounced founder effect, as 17 of 30 (57%) pathogenic ATM alleles in the patients of Slavic origin were represented by three recurrent mutations (c.5932G > T, c.450_453delTTCT, and c.1564_1565delGA). These data have to be taken into account while considering the genetic diagnosis and screening for ataxia-telangiectasia syndrome.

Keywords: Ataxia-telangiectasia; Founder effect; Mutation.

MeSH terms

  • Adolescent
  • Ataxia Telangiectasia / epidemiology
  • Ataxia Telangiectasia / genetics*
  • Ataxia Telangiectasia / pathology
  • Ataxia Telangiectasia Mutated Proteins / genetics*
  • Child
  • Child, Preschool
  • Female
  • Founder Effect
  • Genetic Predisposition to Disease*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Male
  • Russia / epidemiology


  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins