Objective: Common variable immunodeficiency (CVID) is a type of inborn errors of immunity (IEI) characterized by antibody deficiency, recurrent infections, autoimmunity, autoinflammation, lymphoproliferation, and malignancy, representing a broad phenotypic spectrum. Unlike other subgroups, only about 10% of CVID cases have a detectable genetic etiology, suggesting a complex inheritance pattern for this group. However, in cases with early onset, a positive family history and consanguinity with monogenic inheritance is considered likely. This study aimed to investigate the genetic etiology in patients diagnosed with CVID.

Materials and Methods: This study included 27 patients classified as CVID based on ESID diagnostic criteria, who were followed for antibody deficiency in our clinic between 2000 and 2017. Whole exome sequencing (WES) or gene panel sequencing was performed for each patient. For cases where standard analysis yielded no results, copy number variation (CNV) analysis was applied.

Results: The median age of diagnosis for patients included in the study was 11 years, with a consanguinity rate of 46%. Genetic factors were identified in 13 patients (48.1%). Whole exome sequencing was performed in 73% of the patients, while 37% underwent gene panel sequencing. In 8 cases with detected mutations, standard analysis was sufficient, but CNV analysis provided the result in 2 cases. In 2 patients, BTK mutations associated with X-linked agammaglobulinemia (XLA) were detected, and ICOS mutations were identified in another 2 patients. Heterozygous mutations in NFKB1 and NFKB2 were found in 2 patients without consanguinity or a family history. Mutations in IGLL1 and IGHM, two known causes of autosomal recessive agammaglobulinemia, were found in 2 patients with early onset and positive family history. In one patient with EBV-associated lymphoma, an ADA2 mutation was identified.

Conclusion: Although the efficacy of next-generation sequencing in CVID diagnosis is reported to be limited, we observed a higher prevalence of monogenic forms of CVID in our country, where consanguineous marriages are common, compared to the literature.