INTRODUCTION
One of the most common primary immunodeficiencies (PIDs) in children is
Common Variable Immunodeficiency (CVID), which is a polygenic and
heterogenous disorder characterized by recurrent infections,
hypogammaglobulinemia (markedly reduced immunoglobulin (Ig)G serum
concentration in combination with low levels of IgA and/or IgM),
autoimmunity, poor antibody response to immunizations, and absence of
any other defined immunodeficient state, which makes it a diagnosis of
exclusion 1-4. Only 5-25% of individuals with CVID
have an affected relative, with most of them showing an autosomal
dominant (AD) pattern of inheritance 5. Biallelic
mutations in several genes involved in B cell stimulation have been
identified and shown to be associated with autosomal recessive (AR)
hypogammaglobulinemia (CD19 6, MS4A17, CD81 8, CR29, and TNFRSF13C 10). In 2012,
Lopez-Herrera et al. discovered mutations in the LRBA gene
associated with the clinical presentation of CVID for the first time,
which is known as LPS-responsive beige-like anchor protein (LRBA)
deficiency since 1. According to the International
Union of Immunological Societies, LRBA deficiency is classified as a
disease of immune dysregulation due to regulatory T (Treg)-cell defects
since 2018 11.
LRBA is a cytosolic protein in the BEACH-WD40 protein family, which is
expressed in several cell types and tissues 1,12,13.
LRBA participates in multiple cellular processes including cytoskeleton
assembly, signal transduction, vesicular trafficking, transcriptional
regulation, chromatin dynamics, and apoptosis, and has a role in
maintaining intracellular stores of CTLA4 (cytotoxic
T-lymphocyte-associated protein 4) in T-cells 12,14.
However, still little is known about the definitive role of LRBA in
cellular function and human biology, which remains to be clarified1,12,13.
Lopez-Herrera et al. managed to find four distinct homozygous mutations
in the LRBA gene in five symptomatic individuals clinically
diagnosed with CVID 1. Since then, several novel
mutations in the LRBA gene have been identified and shown in many
case reports of PID as well as in other disorders without
hypogammaglobulinemia 15-22. Here, we report a novel
mutation in LRBA in a patient with childhood-onset
immunodeficiency presenting with CVID-like symptoms.