Novel heterozygous mutation in NFKB2 in a patient with predominantly antibody deficiency

Abstract

Background: The Nuclear Factor-kappa B (NF-kB) pathway is a signaling pathway that plays a critical role in regulating a wide range of cellular processes among those such as immune function, inflammation and tumor regulation. There are two major pathways that play a role in NF-kB activation: the canonical NF-kB1 pathway and the non-canonical NF-kB2 pathway. Abnormalities in non-canonical NF-κB signaling are linked with significant impairments in the immune system, mainly B cell maturation, antibody production, impact on T helper and regulatory T cell function through its effect on germinal center regulation. Methods: Our patient's medical record was analyzed retrospectively, including her medical history, as well as results from immune laboratory tests and genetic analyses. Results: We present a 16-year-old female with a history of chronic cough complicated with episodes of hemoptysis and diagnosed with bronchiectasis secondary to common variable immunodeficiency disease. Whole exome sequence analysis revealed a novel heterozygous variant in the NFKB2 gene (NM_001077494.3), c.931C>T resulting in p. Arg567Cys. Conclusion: The presence of NFKB2 mutations can lead to the development of early-onset common variable immunodeficiency. Statement of Novelty: We have identified a novel variant in the NFKB2 gene associated with antibody deficiency.