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| Inflammatory bowel disease v1.3 | AIRE |
Tiarni Templeton gene: AIRE was added gene: AIRE was added to Inflammatory bowel disease. Sources: Literature,Expert Review Mode of inheritance for gene: AIRE was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: AIRE were set to 37067225; 23314667 Phenotypes for gene: AIRE were set to Autoimmune polyendocrinopathy syndrome , type I, with or without reversible metaphyseal dysplasia Penetrance for gene: AIRE were set to Complete Review for gene: AIRE was set to GREEN Added comment: Is currently in the congenital diarrhoea panel but not in IBD panel which we use for our VEO-IBD patients or treatment refractory patients; recommend including in IBD panel. Sources: Literature, Expert Review |
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| Inflammatory bowel disease v0.126 | OTUD3 |
Peter McNaughton gene: OTUD3 was added gene: OTUD3 was added to Inflammatory bowel disease. Sources: Literature Mode of inheritance for gene: OTUD3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: OTUD3 were set to PMID: 41067575 Phenotypes for gene: OTUD3 were set to Ulcerative colitis Review for gene: OTUD3 was set to AMBER Added comment: Multigenerational family with a medically refractory colitis phenotype permitted identification of the A143T missense mutation in OTUD3 as the causal variant. Murine model replicating phenotype and demonstrating impaired intestinal barrier function. Amber for single kindred. Sources: Literature |
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| Inflammatory bowel disease v0.59 | IFIH1 |
Sarah Pantaleo changed review comment from: Rare, likely loss-of-functions IFIH1 variants identified in eight patients with Very Early Onset Inflammatory Bowel Disease (VEOIBD) with VEOIBD from a combined cohort of 42 children. One homozygous truncating variant in a neonate from a consanguineous family, seven carriers of LoF variants (three of whom also have a second hypomorphic missense variant). Luciferase reporter assays employed to assess MDA5 activity (encoded by IFIH1). In three cases, the functional studies demonstrated that the second missense variant either did not affect protein function or was in cis with the LoF variant. Sources: Literature; to: IFIH1 encodes MDA5, a key cystolic sensor for viral nucleic acids. Rare, likely loss-of-functions IFIH1 variants identified in eight independent probands with Very Early Onset Inflammatory Bowel Disease (VEOIBD) from a combined cohort of 42 children. IFIH1 variants were significantly enriched in children with VEOIBD as compared to controls (p=0.007). In one case of neonatal-onset IBD, a homozygous truncating variant was identified. There were seven carriers of LoF variants identified (range of onset 6 months to 6 years of age). In three of these cases, a second hypomorphic missense variant was identified. Luciferase reporter assays were employed to assess MDA5 activity. In some cases, the second missense variant was either proven to not affect protein function or was in cis with the LoF variant. Complete and partial MDA5 deficiency is associated with VEOIBD with variable penetrance and expressivity, suggesting a role for impaired intestinal viral sensing in IBD pathogenesis. Sources: Literature |
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