%0 Journal Article
%A Dhingani, Neel
%A Guo, Conghui
%A Pan, Jie
%A Li, Qi
%A Warner, Neil
%A Jardine, Sasha
%A Leung, Gabriella
%A Kotlarz, Daniel
%A Gonzaga-Jauregui, Claudia
%A Klein, Christoph
%A Snapper, Scott B.
%A Navas-López, Víctor Manuel
%A Muise, Aleixo M.
%T The E3 ubiquitin ligase UBR5 interacts with TTC7A and may be associated with very early onset inflammatory bowel disease
%D 2020
%U http://hdl.handle.net/10668/3886
%X 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.
%K Child
%K Amino acid sequence
%K Inflammatory bowel diseases
%K Protein binding
%K Ubiquitin-protein ligases
%K Colitis
%K Niño
%K Secuencia de aminoácidos
%K Enfermedades inflamatorias del intestino
%K Unión proteica
%K Ubiquitina-proteína ligasas
%~