Our cases and literature review further expand existing knowledge on the phenotype and <i>TRNT1</i> variations of SIFD and suggest that the early genomic diagnosis of <i>TRNT1</i> is valuable to promptly assess bone marrow transplantation and tumor necrosis factor inhibitor treatments, which might be effective for the immunodeficiency and inflammation caused by SIFD. The gene discussed is TNF; the disease is Immunodeficiency.