Transient immune deficiency accompanied with homozygous CBL rare variant

Abstract Background A critical role in cellular proliferation is played by Casitas B‐lineage Lymphoma proto‐oncogene (CBL). Germline heterozygous CBL variants give rise to CBL syndrome, which is phenotypically similar to RASopathy. Somatic mutations in CBL have been reported in patients with juvenile myelomonocytic leukemia (JMML). Methods Exome analysis was performed in a patient with immunodeficiency who developed Pneumocystis jirovecii pneumonia. Results Exome analysis identified a homozygous CBL missense variant. Cell biological analysis of this CBL variant confirmed attenuated function. Conclusion Spontaneous regression of hematological proliferation has been observed in patients with CBL ‐mutated JMML and in patients with CBL syndrome. Intriguingly, immunological impairment was spontaneously ameliorated by aging in this patient.