*Article* **Common Variable Immunodeficiency Associated with a De Novo** *IKZF1* **Variant and a Low Humoral Immune Response to the SARS-CoV-2 Vaccine**

**Irene Díaz-Alberola 1,2,3,\*, Andrea Espuch-Oliver 4, José María García-Aznar 5, Christian Ganoza-Gallardo 5, María Aguilera-Franco 6, Antonio Sampedro 6, Pilar Jiménez 1,2 and Miguel Ángel López-Nevot 1,2,7**


**Abstract:** Background and Aims: Common variable immunodeficiency (CVID) comprises a group of diseases with heterogeneous clinical and immunological manifestations. Several mutations have been identified in genes encoding proteins essential for immune function. Our aim was to phenotypically and genotypically characterize a patient diagnosed with CVID and study his response to the SARS-CoV-2 vaccine. Methods: We performed a next-generation sequencing analysis, a CMIA, and an ELISA to analyze the humoral and cellular response to the SARS-CoV-2 vaccine, respectively. We also employed flow cytometry and immunoturbidimetry to assess the patient's global immune status. Results: We found a low humoral but positive cellular response to the SARS-CoV-2 vaccine. NGS screening revealed a transition from guanine to adenine at position c.485 of the *IKZF1* gene in heterozygosity, giving rise to the R162Q variant, which was not present in his parents. Conclusions: The R162Q variant of the *IKZF1* gene has been associated with CVID type 13, but always with an autosomal dominant inheritance with high penetrance. Therefore, we present for the first time a case of CVID associated with a de novo heterozygous R162Q variant in the *IKZF1* gene in a patient with a low humoral immune response to the complete COVID-19 vaccination program.

**Keywords:** CVID; *IKZF1*; IKAROS; de novo mutation; R162Q; immune response; SARS-CoV-2; heterologous vaccine; humoral response; T-cell response
