# Genetic Mosaicism in Inborn Errors of Immunity

> **NIH NIH R21** · WASHINGTON UNIVERSITY · 2022 · $196,875

## Abstract

Project Summary
Inborn errors of immunity (IEI) are a heterogeneous group of disorders due to monogenic defects in the
immune response that have a broad clinical spectrum including susceptibility to infection, autoimmunity,
inflammation, and cancer susceptibility. There are more than 450 distinct IEI that have been discovered.
Diagnosis of the precise genetic cause and mechanism (e.g., gain-of-function or loss-of-function) of IEI has led
to enhanced care and treatment of patients through improved diagnosis, guidance for clinical monitoring based
on genotype, and targeted therapies. While discovery of new IEI and testing for patients has rapidly grown,
successful genetic diagnosis still only occurs for ~40% of the patients identified by expert clinicians as likely to
have monogenic disease. However, IEI can also arise from de novo mutations in somatic cells, i.e., post-
zygotic genetic changes in DNA sequence that may be missed by current sequencing approaches. This
mosaic disease can phenocopy germline disease, particularly for disorders with a ‘dominant’ phenotype. We
will address this gap through development of a strategy to detect and validate mosaic genetic variants. In Aim
1, we will use a custom capture sequencing assay to identify mosaicism in known and predicted IEI genes in
patients who remain undiagnosed despite standard testing. In Aim 2, we will functionally validate mosaic
variants using single cell sequencing techniques to correlate genotype with expression profile. The long-term
goal of this application is to improve diagnosis of IEI to enable diagnosis and targeted therapy of patients with
these disorders.

## Key facts

- **NIH application ID:** 10432960
- **Project number:** 1R21AI168957-01
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** MEGAN Anne COOPER
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $196,875
- **Award type:** 1
- **Project period:** 2022-02-03 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10432960

## Citation

> US National Institutes of Health, RePORTER application 10432960, Genetic Mosaicism in Inborn Errors of Immunity (1R21AI168957-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10432960. Licensed CC0.

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