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Review
. 2025 Mar;155(3):759-767.
doi: 10.1016/j.jaci.2024.11.038. Epub 2024 Dec 24.

Somatic mosaicism in genetic errors of immunity

Megan A Cooper  1
Affiliations
Review

Somatic mosaicism in genetic errors of immunity

Megan A Cooper. J Allergy Clin Immunol. 2025 Mar.

Abstract

Genetic mosaicism in somatic cells can lead to the presence of pathogenic variants in a subset of immune cells causing genetic errors of immunity, often phenocopying germline inborn errors of immunity. Over the last 2 decades, significant progress has been made in the identification of these disorders in patients, including discovery of new diseases. Diagnosis of disease-causing somatic mosaicism provides a target for treatment and monitoring of patients and has implications for genetic counseling. However, there continue to be barriers in the identification of somatic mosaicism, particularly for the clinical diagnosis of patients, based on the limitations of current diagnostic sequencing and analysis approaches. This review focuses on how somatic mosaicism can lead to genetic errors of immunity, the genes known to be associated with somatic genetic errors of immunity, and challenges in the field for accurate diagnosis of patients.

Keywords: Primary immunodeficiencies; genetic; immune dysregulation; inborn errors of immunity; mosaic; somatic.

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Conflict of interest statement

Disclosure statement Work in the Cooper lab was supported by National Institutes of Health (NIH) National Institute of Allergy and Infectious Diseases grant R21AI168957. The content is solely the responsibility of the author and does not necessarily represent the official views of the NIH. This work was supported by the Children’s Discovery Institute Center for Pediatric Immunology at Washington University and St Louis Children’s Hospital, and the Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies at St Louis Children’s Hospital. Disclosure of potential conflict of interest: The author declares that she has no relevant conflicts of interest.

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