Background: IFN regulatory factor 2 binding protein 2 (IRF2BP2) was identified as an IRF-2-dependent transcriptional corepressor binding to the C-terminal repression domain of IRF2. IRF2BP2 also could bind to the C‑terminus of nuclear factor of activated T cells (NFAT1) and act as a regulator of NFAT-responsive genes transcription. IRF2BP2 was described as an important transcriptional cofactor regulating various biological systems including cell cycle, apoptosis, immune responses, cell differentiation, inflammation and angiogenesis. More recently, it has been shown that IRF2BP2 mutations could cause autosomal‑dominant common variable immunodeficiency (CVID). CVID as a syndrome comprises a heterogeneous group of diseases, characterized by recurrent infections due to significant hypogammaglobulinemia.
Methods: Whole exome sequencing and targeted next‑generation sequencing was performed with genomic DNA isolated from whole blood.
Results: In our study we identified four novel monoallelic IRF2BP2 variants in five patients within a CVID cohort. Novel monoallelic missense mutations were detected in one male patient (c.352C>T; p.P118S) and two affected sisters from non‑consanguineous parents (c.1645T>G; p.C549G). One patient was identified with a stop‑gain mutation (c.1615_1616delinsT; p.K539Yfs*41), which is predicted to cause a truncation of protein length due to a premature termination of translation. Another patient harbored an in‑frame deletion variant (c.293_295delAGC; p.Q94del).
Conclusions: We identified novel IRF2BP2 mutations in a family with autosomal dominant CVID and in three sporadic CVID cases. Monoallelic IRF2BP2 mutations may cause monogenic CVID with different clinical manifestations and onset.