title: Genetic basis and pancreatic biology of Johanson-Blizzard syndrome.
abstract: The most recent elucidation of an inherited disorder of the pancreas concerns the Johanson-Blizzard syndrome (JBS). Positional cloning identified loss-of-function mutations in the UBRI gene on the long arm of chromosome 15 to be the cause of JBS in more than a dozen patients. In patients with JBS the absence of UBRI results in early prenatal destruction of the exocrine pancreas that involves impaired apoptosis, induced necrosis, and prominent inflammation. Knockout mice with absent UBR1 expression suffer from exocrine pancreatic insufficiency and increased susceptibility to experimental pancreatitis. The UBR1 protein substrate, presumably impaired degradation of which causes JBS, is not yet known.
authors.affiliation: Institute of Human Genetics, University of Erlangen-Nuremberg, Schwabachanlage 10, 91054 Erlangen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Zenker
authors.forename: Julia
authors.initials: J
authors.lastname: Mayerle
authors.forename: André
authors.initials: A
authors.lastname: Reis
authors.forename: Markus M
authors.initials: MM
authors.lastname: Lerch
mesh_terms: D000015:Abnormalities, Multiple / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D010188:Exocrine Pancreatic Insufficiency / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D006311:Hearing Disorders / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology; D006801:Humans; D008607:Intellectual Disability / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D020125:Mutation, Missense / Q000235:genetics / Q000502:physiology; D044767:Ubiquitin-Protein Ligases / Q000235:genetics* / Q000378:metabolism
chemical_list: C113474:UBR1 protein, human; D044767:Ubiquitin-Protein Ligases