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

FIRTINA S., Saritas M., Ng Y. Y., Nepesov S., KIYKIM A., Bozkurt S., ...More

Immunologic Research, vol.73, no.1, 2025 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 73 Issue: 1
  • Publication Date: 2025
  • Doi Number: 10.1007/s12026-025-09638-1
  • Journal Name: Immunologic Research
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CAB Abstracts, EMBASE, MEDLINE, Veterinary Science Database
  • Keywords: Ataxia-telangiectasia, ATM gene, Genetic diagnosis, Severe combined immunodeficiency, T-cell lymphopenia
  • Abdullah Gül University Affiliated: No

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.