Genetic basis and pancreatic biology of Johanson-Blizzard syndrome.
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.
Zenker
Martin
M
Institute of Human Genetics, University of Erlangen-Nuremberg, Schwabachanlage 10, 91054 Erlangen, Germany.
Mayerle
Julia
J
Reis
André
A
Lerch
Markus M
MM
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
C113474:UBR1 protein, human; D044767:Ubiquitin-Protein Ligases