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Primary immunodeficiency or monogenic inflammatory bowel disease v9.83 SIT1 Achchuthan Shanmugasundram Classified gene: SIT1 as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v9.83 SIT1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is only one case and functional evidence reported in support of the association of SIT1 gene with combined immunodeficiency. Hence, this gene should be rated amber with the current evidence.
Primary immunodeficiency or monogenic inflammatory bowel disease v9.83 SIT1 Achchuthan Shanmugasundram Gene: sit1 has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v9.82 SIT1 Achchuthan Shanmugasundram Phenotypes for gene: SIT1 were changed from Combined immunodeficiency; Hodgkin lymphoma; Abnormal T cell physiology; Impaired CD8+ T cell cytotoxicity to combined immunodeficiency, MONDO:0015131
Primary immunodeficiency or monogenic inflammatory bowel disease v9.81 SIT1 Achchuthan Shanmugasundram reviewed gene: SIT1: Rating: AMBER; Mode of pathogenicity: None; Publications: 42128181; Phenotypes: combined immunodeficiency, MONDO:0015131; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v9.15 SIT1 Boaz Palterer gene: SIT1 was added
gene: SIT1 was added to Primary immunodeficiency or monogenic inflammatory bowel disease. Sources: Literature
Mode of inheritance for gene: SIT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SIT1 were set to 42128181
Phenotypes for gene: SIT1 were set to Combined immunodeficiency; Hodgkin lymphoma; Abnormal T cell physiology; Impaired CD8+ T cell cytotoxicity
Penetrance for gene: SIT1 were set to unknown
Review for gene: SIT1 was set to RED
Added comment: Pu Chen et al. described 1 patient from 1 kindred, harboring homozygous mutations in the SIT1 gene. They presented with combined immune deficiency and recurrent Hodgkin lymphoma. The underlying mechanism and phenotype were validated ex vivo using patient-derived lymphocytes and in vitro using CRISPR-Cas9-mediated SIT1 knockout T cells from healthy donors, demonstrating skewed T cell subsets, increased activation and proliferation, impaired CD8+ cytotoxicity, and defective immune synapse maturation with vesicle accumulation upon T cell receptor stimulation. The phenotype was successfully recreated with complete knockout models.
Sources: Literature