Novel genetic variants of inborn errors of immunity

PLoS One. 2021 Jan 22;16(1):e0245888. doi: 10.1371/journal.pone.0245888. eCollection 2021.


Objectives: Inborn errors of immunity (IEI) are prevalent in tribal cultures due to frequent consanguineous marriages. Many of these disorders are autosomal recessive, resulting from founder mutations; hence they are amenable to prevention. The primary objective of this study was to evaluate the pathogenicity of novel variants of IEI found among Emiratis.

Methods: This retrospective data collection study reports novel variants of IEI detected by diagnostic exome sequencing. Pathogenicity prediction was based on scoring tools, amino acid alignment, and Jensen-Shannon divergence values.

Results: Twenty-one novel variants were identified; nine were frameshift, three nonsense, four intronic (one pathogenic), and five missense (two pathogenic). Fifteen variants were likely pathogenic, of which 13 were autosomal recessive and two uncertain inheritance. Their clinical spectra included combined immunodeficiency, antibody deficiency, immune dysregulation, defects in intrinsic/innate immunity, and bone marrow failure.

Conclusion: The described novel pathogenic variants are core to a planned national screening program that aims toward IEI prevention. Future studies, however, are needed to confirm their natural history in individual patients and estimate their prevalence in the community.

MeSH terms

  • Animals
  • Bone Marrow Failure Disorders / genetics
  • Computational Biology
  • Genetic Diseases, Inborn / genetics*
  • Genetic Diseases, Inborn / immunology*
  • Genetic Variation*
  • Herpesvirus 4, Human / physiology
  • Humans
  • Immunity, Innate / genetics
  • Lymphohistiocytosis, Hemophagocytic / genetics
  • Retrospective Studies

Grants and funding

This retrospective data collection study has no source of funding. The study has not received any funding from grants, organizations, or institutions (including our institution). The authors received no specific funding for this work. We have no conflicts of interest to disclose. This manuscript is not funded.