IKAROS, a transcription factor encoded by IKZF1, is expressed during hematopoiesis that is implicated in lymphocyte and myeloid differentiation and negative regulation of cell proliferation. Recently, heterozygous germline IKZF1 mutations have been identified in patients with a B cell immune deficiency mimicking common variable immunodeficiency. Herein, we report a patient with common variable immunodeficiency associated with germline missense IKZF1 heterozygous mutation.
The targeted new generation sequencing PID V1 panel was used.
A 20-year-old male patient who was born to non-consanguineous parents presented with recurrent bacterial upper and lower respiratory tract infection, anemia and chronic diarrhea. Physical examination was normal. Laboratory tests revealed anemia, hypogammaglobulinemia and B cell lymphopenia. In B cell subsets memory B cell, switch memory B cell, marginal zone memory B cell were low. Vaccine responses and isohemagglutinin tests were poor. Colonoskopy was perfermed and revealed as inflammatory bowel disease. The genetic analysis revealed germline missense IKZF1 heterozygous mutation affecting amino acid T510A located in the Zn_C2H2 domain of IKZF1.
Germline heterozygous IKZF1 mutations cause hypogammaglobulinemia, hematologic abnormalities, including B-cell defect; and autoinflammatory diseases.