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oai:repisalud.isciii.es:20.500.12105/181392024-11-28T15:19:57Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927
Repisalud author Dhingani, Neel author Guo, Conghui author Pan, Jie author Li, Qi author Warner, Neil author Jardine, Sasha author Leung, Gabriella author Kotlarz, Daniel author Gonzaga-Jauregui, Claudia author Klein, Christoph author Snapper, Scott B. author Navas-López, Víctor Manuel author Muise, Aleixo M. authoraffiliation [Dhingani,N; Jardine,S; Muise,AM] Department of Biochemistry, Faculty of Medicine, University of Toronto, Toronto, ON, Canada. [Dhingani,N; Guo,C; Pan,J; Li,Q; Warner,N; Jardine,S; Leung,G; Muise,AM] SickKids Infammatory Bowel Disease Centre, Research Institute, Hospital for Sick Children, Toronto, ON, Canada. [Kotlarz,D; Klein,C] Department of Pediatrics, Dr. Von Hauner Children’s Hospital, University Hospital, LMU Munich, Munich, Germany. [Gonzaga-Jauregui,C] Regeneron Genetics Center, Regeneron Pharmaceuticals Inc., Tarrytown, NY, USA. [Snapper,SB] Division of Gastroenterology, Hepatology and Nutrition, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA. [Navas-López,VM] Pediatric Gastroenterology and Nutrition Unit, IBIMA, Hospital Regional Universitario de Málaga, Málaga, Spain. [Muise,AM] Cell Biology Program, Research Institute, The Hospital for Sick Children, Toronto, ON, Canada. [Muise,AM] Department of Pediatrics, Institute of Medical Science, University of Toronto, Toronto, Canada. [Snapper,SB] Division of Gastroenterology, Brigham and Women’s Hospital, Boston, MA, USA. 2024-02-12T19:47:42Z 2024-02-12T19:47:42Z 2020-10-29 10.1038/s41598-020-73482-6 2045-2322 Scientific Reports http://hdl.handle.net/10668/3886 33122718 http://hdl.handle.net/20.500.12105/18139 Very 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. eng Child Amino acid sequence Inflammatory bowel diseases Protein binding Ubiquitin-protein ligases Colitis Niño Secuencia de aminoácidos Enfermedades inflamatorias del intestino Unión proteica Ubiquitina-proteína ligasas The E3 ubiquitin ligase UBR5 interacts with TTC7A and may be associated with very early onset inflammatory bowel disease research article