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Updated: Jul 12, 2025
Assessing Somatic Hypermutation in Ramos B Cells after Overexpression or Knockdown of Specific Genes
Published on: November 1, 2011
A novel homozygous mutation in RASGRP1 that predisposes to immune dysregulation and immunodeficiency associated with
Rana Mansour1, Youmna El-Orfali1, Adam Saidu1
1Department of Experimental Pathology, Immunology, and Microbiology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
Background:
RASGRP1-deficiency results in an immune dysregulation and immunodeficiency that manifest as autoimmunity, lymphoproliferation, lymphopenia, defective T cell function, and increased incidence of Epstein-Bar Virus infections and lymphomas.
Objective:
To investigate the mechanism of autoimmune hemolytic anemia and infections in a male patient of consanguineous parents from Lebanon.
Methods:
Genetic diagnosis was obtained using next generation and Sanger sequencing. Protein expression and phosphorylation were determined by immunoblotting. T and B cell development and function were studied by flow cytometry. Cytokine and immunoglobulin secretions were quantified by enzyme-linked immunosorbent assay.
Results:
The patient suffered from severe lymphopenia especially affecting the T cell compartment. Genetic analysis revealed a homozygous insertion of adenine at position 1396_1397 in RASGRP1 that abolished protein expression and downstream Ras signaling. T cells from the patient showed severe activation defects resulting in uncontrolled Epstein-Bar Virus-induced B cell proliferation. B cells from the patient were normal.
Conclusion:
This report expands the spectrum of mutations in patients with RasGRP1 deficiency, and provides evidence for the important role RasGRP1 plays in the ability of T cells to control Epstein-Bar Virus-induced B cell proliferation.
Clinical Implications:
Following diagnosis, the patient will be maintained on oral valganciclovir and monitored regularly for Epstein-Bar Virus infections to avoid the development of Epstein-Bar Virus- induced B cell lymphoma. He is also candidate for hematopoietic stem cell transplantation.
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