Dhingani, NeelGuo, ConghuiPan, JieLi, QiWarner, NeilJardine, SashaLeung, GabriellaKotlarz, DanielGonzaga-Jauregui, ClaudiaKlein, ChristophSnapper, Scott B.Navas-López, Víctor ManuelMuise, Aleixo M.2024-02-122024-02-122020-10-29http://hdl.handle.net/10668/3886http://hdl.handle.net/20.500.12105/18139Very early onset inflammatory bowel disease (VEOIBD) denotes children with onset of IBD before six years of age. A number of monogenic disorders are associated with VEOIBD including tetratricopeptide repeat domain 7A (TTC7A) deficiency. TTC7A-deficiency is characterized by apoptotic colitis in milder cases with severe intestinal atresia and immunodeficiency in cases with complete loss of protein. We used whole exome sequencing in a VEOIBD patient presenting with colitis characterized by colonic apoptosis and no identified known VEOIBD variants, to identify compound heterozygous deleterious variants in the Ubiquitin protein ligase E3 component N-recognin 5 (UBR5) gene. Functional studies demonstrated that UBR5 co-immunoprecipitates with the TTC7A and the UBR5 variants had reduced interaction between UBR5 and TTC7A. Together this implicates UBR5 in regulating TTC7A signaling in VEOIBD patients with apoptotic colitis.engVoRhttp://creativecommons.org/licenses/by/4.0/ChildAmino acid sequenceInflammatory bowel diseasesProtein bindingUbiquitin-protein ligasesColitisNiñoSecuencia de aminoácidosEnfermedades inflamatorias del intestinoUnión proteicaUbiquitina-proteína ligasasAge of OnsetAmino Acid SequenceChild, PreschoolHumansInflammatory Bowel DiseasesMaleProtein BindingProteinsSequence Homology, Amino AcidSignal TransductionUbiquitin-Protein LigasesColitisAttribution 4.0 International3312271810.1038/s41598-020-73482-62045-2322Scientific Reportsopen access