Aims: Common Variable Immunodeficiency (CVID) is a heterogeneous primary immunodeficiency characterized by impaired antibody production and diverse clinical manifestations. Although some monogenic causes are known, the genetic basis remains unclear for many patients. This retrospective study aimed to investigate the presence of pathogenic or potentially pathogenic genetic variants in CVID patients and compare their clinical, demographic, and laboratory features with those without such variants.Methods: A total of 68 CVID patients were divided into two groups based on their genetic analysis results: the mutation present group, including patients with pathogenic, likely pathogenic, or variants of uncertain significance (VUS) with potential pathogenicity; and the mutation absent group, including those with benign/likely benign variants or no mutations. Clinical and laboratory data were collected from patient records and compared statistically.Results: Twenty-five patients (36.7%) were in the mutation present group, and 43 (63.3%) were in the mutation absent group. Serum IgG levels were significantly higher in the mutation present group (p = 0.013). Splenomegaly (52% vs. 20.9%, p = 0.008) and cytopenia (64% vs. 23.3%, p = 0.001) were more frequent in the mutation present group. Multivariate analysis showed that absence of bronchiectasis (OR = 4.208, p = 0.036), presence of splenomegaly (OR = 3.699, p = 0.047), cytopenia (OR = 6.632, p = 0.004), and rheumatologic disease (OR = 6.811, p = 0.028) independently predicted mutation presence.Conclusion: Splenomegaly, cytopenia, and rheumatologic disease independently predicted mutation presence in CVID patients, suggesting a link between genetic variants and immune dysregulation. Despite CVID’s heterogeneity, some patients have identifiable genetic backgrounds tied to distinct clinical features. Larger prospective studies are needed to clarify genotype–phenotype correlations. Detecting genetic defects is also crucial for patient care and family risk assessment.
Akkuş et al. (Tue,) studied this question.