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Approved Research

Associations between CXCR4 genetic variants and immunodeficiency phenotypes

Principal Investigator: Dr Katarina Zmajkovicova
Approved Research ID: 81315
Approval date: February 8th 2022

Lay summary

Primary immunodeficiencies (PIDs) are a group of inherited diseases that result in impairment of normal immune system function. The affected individuals often suffer from recurrent infections. Warts, Hypogammaglobulinemia, Infections and Myelokathexis (WHIM) syndrome, one such PID, causes different symptoms including low immune cell counts in blood, bacterial infections or skin warts and it is caused by mutations in the C-X-C chemokine receptor type 4 (CXCR4) gene.  Currently there is a small number of pathogenic mutations in CXCR4 that are known to cause WHIM syndrome. Novel CXCR4 mutations are sometimes identified in patients with immunodeficiency, but due to  missing information on their pathogenicity, the diagnosis of WHIM syndrome cannot be confirmed. As a result, these individuals may not be eligible for the best suitable treatment. We plan to look at a large group of people in the UK Biobank to identify individuals who have CXCR4 mutations  as well as low blood cell counts or other signs of immunodeficiency. We will analyze these mutations in laboratory tests and then combine all data to conclude which of the mutations are likely to cause decreased immune system function. This study will form the foundations for better diagnosis of WHIM syndrome or other CXCR4-related immunodeficiency. The project will last for one year.