NF-κB1 haploinsufficiency due to a novel c.104delT variant in two patients with common variable immunodeficiency.

Common variable immunodeficiency (CVID) is the most frequent clinically relevant inborn error of immunity. Genetic defects can be identified in one-third of cases. The identification of novel mutations remains crucial for understanding disease mechanisms and genotype-phenotype correlations. We report a 19-year-old female with recurrent infections, hepatomegaly, and lymphadenopathy that began one year before the assessment. Laboratory evaluation revealed neutropenia, lymphopenia, anemia, thrombocytopenia, hypogammaglobulinemia, and a reduced percentage of switched memory B cells. Next-generation sequencing identified a previously unreported NFKB1 c.104delT nonsense mutation and a heterozygous CFTR F508del variant. The patient's mother also exhibited recurrent infections, anemia, hypogammaglobulinemia, and a low percentage of switched memory B cells, which started when she was 25 years old. Genetic testing revealed the same NFKB1 mutation. The identified NFKB1 variant has not been described in available databases. The predicted loss-of-function effect, along with the patients' phenotypes, supports its pathogenic relevance. This report expands the mutational spectrum of NFKB1 and underscores the importance of detailed genetic assessment in patients with immunodeficiency and immune dysregulation.