Heterozygous Frameshift Genetic Variant in TNFRSF13C Gene Associated with Specific Antibody Deficiency Memory Phenotype
DOI:
https://doi.org/10.71332/5y3gtw10Keywords:
Specific Antibody Deficiency, BAFFR, TNFRSF13CAbstract
Specific antibody deficiency (SAD) is a primary immunodeficiency disease (PID) in which patients present with recurrent sinopulmonary bacterial infections and decreased antibody responses to polysaccharide antigens following vaccination. SAD memory phenotype refers to an initial serologic and clinical response to the 23-valent polysaccharide vaccine followed by the loss of protective antibodies within six months. Various PID can present with diminished specific antibody responses, and it is known that patients with SAD can develop Common Variable Immunodeficiency (CVID) later in life. We present the case of a 7-year-old male with significant history of recurrent sinopulmonary infections since the age of two, who was diagnosed with SAD memory phenotype. A PID genetic panel revealed a TNFRSF13C genetic variant of unknown significance in Exon 3: c.534_543delinsAATAGCAGG (p.Ala179Ilefs*46). This variant results in a frameshift in the B cell-activating factor receptor (BAFFR) encoding gene. BAFFR is essential for the survival and maturation of transitional B cells into mature follicular and marginal zone B cells and has an important role in the development of T-independent antibody responses. BAFFR deficiency is known to be a genetic etiology for CVID and heterozygous missense polymorphisms have been implicated as risk factors for the development of CVID. The patient’s phenotype, which demonstrates inadequate T-independent antibody responses, correlates with the previously described phenotype of patients with TNFRSF13C variants. Here, we present a patient with SAD memory phenotype harboring a frameshift heterozygous variant in BAFFR. This case highlights the need to consider rare genetic causes in patients with PID.
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Copyright (c) 2026 Mariana Acuña, Dr. De Jesús Rojas, Dr. Fernández Dávila (Author)
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