Identification of nonsense variants in the ATM gene mimicking SCID phenotype: a brief report

Immunol Res. 2025 May 16;73(1):82. doi: 10.1007/s12026-025-09638-1.

Abstract

Severe combined immunodeficiency (SCID) represents a life-threatening inborn error of immunity, necessitating rapid diagnosis and intervention to prevent fatal outcomes. While SCID is characterized by profound T-cell lymphopenia, it may overlap with other conditions like ataxia-telangiectasia (AT), which also presents with T-cell deficiencies. This study examines two cases of suspected SCID in infants, later identified as AT due to pathogenic variants in the ATM gene. Despite initial negative results from SCID-targeted gene panels, further genetic testing revealed nonsense mutations (p.Y2036X and p.E1996X) in the FAT domain of the ATM gene, confirmed by Sanger sequencing. The patients exhibited significant T-cell lymphopenia and reduced ATM protein activity, indicative of AT. These findings highlight the importance of comprehensive genetic screening beyond common SCID-associated genes, especially in patients with atypical presentations. Early and accurate diagnosis can prevent mismanagement and guide appropriate therapies, improving patient outcomes.

Keywords: ATM gene; Ataxia-telangiectasia; Genetic diagnosis; Severe combined immunodeficiency; T-cell lymphopenia.

Publication types

  • Case Reports

MeSH terms

  • Ataxia Telangiectasia Mutated Proteins* / genetics
  • Ataxia Telangiectasia* / diagnosis
  • Ataxia Telangiectasia* / genetics
  • Codon, Nonsense*
  • Female
  • Genetic Testing
  • Humans
  • Infant
  • Male
  • Phenotype
  • Severe Combined Immunodeficiency* / diagnosis
  • Severe Combined Immunodeficiency* / genetics
  • T-Lymphocytes / immunology

Substances

  • Codon, Nonsense
  • Ataxia Telangiectasia Mutated Proteins
  • ATM protein, human