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Primary immunodeficiency or monogenic inflammatory bowel disease v9.9 SH2B3 Boaz Palterer gene: SH2B3 was added
gene: SH2B3 was added to Primary immunodeficiency or monogenic inflammatory bowel disease. Sources: Literature,Expert list
Mode of inheritance for gene: SH2B3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SH2B3 were set to 37206266
Phenotypes for gene: SH2B3 were set to Myeloproliferative disorder; Autoimmunity; Hepatosplenomegaly; Thrombosis; Autoimmune thyroiditis; Autoimmune hepatitis; Global developmental delay
Penetrance for gene: SH2B3 were set to unknown
Review for gene: SH2B3 was set to RED
Added comment: Blombery et al. described 2 patients from 2 kindreds, harboring biallelic loss-of-function mutations in the SH2B3 gene. They presented with early-onset developmental delay, hepatosplenomegaly, multi-organ autoimmunity (including autoimmune thyroiditis and hepatitis), bone marrow myeloproliferation, and severe thrombotic complications. The underlying mechanism was validated ex vivo using patient-derived fibroblasts, demonstrating that upon stimulation with various cytokines (including IL-3, GH, GM-CSF, and EPO), the mutant cells exhibited significantly increased phosphorylation and hyperactivation of JAK2 and STAT5 signaling. The phenotype and mechanism were further validated in vivo using CRISPR-Cas9 engineered zebrafish animal models (sh2b3 F0 crispants). These models successfully recreated the myeloproliferative phenotype, presenting with a significantly increased number of macrophages and thrombocytes. Furthermore, rescue and treatment experiments demonstrated that administering the JAK1/2 inhibitor ruxolitinib to the mutant fish successfully intercepted and resolved the myeloproliferative defect.
Sources: Literature, Expert list
Primary immunodeficiency or monogenic inflammatory bowel disease v5.10 TERC Sarah Leigh Tag locus-type-rna-long-non-coding tag was added to gene: TERC.
Primary immunodeficiency or monogenic inflammatory bowel disease v5.10 TERC Sarah Leigh Tag locus-type-rna-misc was removed from gene: TERC.
Primary immunodeficiency or monogenic inflammatory bowel disease v2.34 TERC Louise Daugherty Source IUIS Classification December 2019 was added to TERC.
Added phenotypes Bone marrow failure, pulmonary and hepatic fibrosis, nail dystrophy, leukoplakia, reticulate skin pigmentation; microcephaly, neurodevelopmental delay; Bone marrow failure for gene: TERC
Publications for gene TERC were updated from 16332973; 11574891; 12525685 to 32048120; 12525685; 16332973; 11574891; 32086639
Primary immunodeficiency or monogenic inflammatory bowel disease TERC Louise Daugherty commented on gene: TERC
Primary immunodeficiency or monogenic inflammatory bowel disease TERC Louise Daugherty marked gene: TERC as ready
Primary immunodeficiency or monogenic inflammatory bowel disease TERC Louise Daugherty commented on gene: TERC
Primary immunodeficiency or monogenic inflammatory bowel disease TERC Louise Daugherty commented on gene: TERC
Primary immunodeficiency or monogenic inflammatory bowel disease TERC Sophie Hambleton reviewed gene: TERC
Primary immunodeficiency or monogenic inflammatory bowel disease TERC Eleanor Williams classified TERC as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease TERC Eleanor Williams commented on gene: TERC
Primary immunodeficiency or monogenic inflammatory bowel disease TERC Eleanor Williams commented on gene: TERC
Primary immunodeficiency or monogenic inflammatory bowel disease TERC Louise Daugherty commented on TERC
Primary immunodeficiency or monogenic inflammatory bowel disease TERC Louise Daugherty classified TERC as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease TERC Louise Daugherty commented on TERC
Primary immunodeficiency or monogenic inflammatory bowel disease TERC Louise Daugherty commented on TERC
Primary immunodeficiency or monogenic inflammatory bowel disease TERC Louise Daugherty reviewed TERC
Primary immunodeficiency or monogenic inflammatory bowel disease TERC Louise Daugherty Added gene to panel
Primary immunodeficiency or monogenic inflammatory bowel disease TERC Louise Daugherty Added gene to panel