Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.4 (trypsin)
 42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

For decades there has been slow progress in understanding pancreatic diseases, particularly acute and chronic pancreatitis. As a result, there were no significant advances in the management of these patients. Treatment was mostly directed towards symptomatic relief and management of complications. A simple clinical observation that multiple members of a large family are affected by acute and chronic pancreatitis, some at very young age and in the absence of any alcohol use, led physician-scientists of the Midwest Multicenter Pancreatic Study Group (investigators from the University of Cincinnati, University of Kentucky, and University of Pittsburgh) to investigate the genetic basis of hereditary pancreatitis. Using information from the human genome project, the hereditary pancreatitis gene was identified as the cationic trypsinogen gene (protease serine 1, PRSS1). This discovery has led to the identification of a number of other genes and their products playing role in the pathogenesis of acute and chronic pancreatitis. In the emerging picture of pathogenesis of acute and chronic pancreatitis, trypsin appears to play a central role. This newly acquired knowledge is setting the stage for new preventive and management strategies for hereditary and sporadic acute and chronic pancreatitis.
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PMID:Lessons from hereditary pancreatitis. 1147 Dec 4

New insight in the field of chronic pancreatitis was provided by the discovery of protease serine 1 (PRSS1) mutation, inherited by autosomal dominant trait in hereditary pancreatitis. Serine protease inhibitor, Kazal type 1 (SPINK1) is a potent protease inhibitor which prevents premature intrapancreatic activation of trypsin and pancreatic autodigestion. Strong associations of SPINK1 mutation and different forms of pancreatitis were suggested. However, it is unlikely that SPINK1 mutation alone can cause chronic pancreatitis. This mutation acts as a disease-modifier or plays a role within polygenic or multifactorial models. A 23 year-old young woman with chronic pancreatitis was recently discovered to have SPINK1 N34S heterozygous mutation cosegregated with two intronic mutations, IVS1-37TC and IVS3-69insTTTT, during the evaluation for potential cause of chronic idiopathic pancreatitis. The same mutation was identified in her mother. This is the first report in Korea suggesting that SPINK1 mutation would be a possible cause of chronic pancreatitis in a patient with familial background.
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PMID:[SPINK1 N34S mutation as a possible cause of chronic pancreatitis in a patient with familial background]. 1764 57

Hereditary pancreatitis is a rare, autosomal dominant, inherited disease characterized by recurrent attacks of acute pancreatitis with the development of chronic pancreatitis and an increased risk of pancreatic cancer. R122H or N29I mutation in cationic trypsinogen (protease serine 1, PRSS1) gene causes hereditary pancreatitis. R122H mutation is the most common mutation that causes pancreatitis by preventing deactivation of trypsin within the pancreas and prolonging its action. Three members of the family, the patient, her elder son, and her niece experienced recurrent attacks of pancreatitis. We analyzed five exons of the PRSS1 gene in DNA samples of five family members including her husband and younger son who were asymptomatic. We found out that four members of the family, the patient, her two sons, and her niece, had R122H mutation in the exon 3 of PRSS1 gene. Finally, we diagnosed hereditary pancreatitis in two households in the same family.
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PMID:[Three cases of hereditary pancreatitis in two households in the same family associated with R122H mutation in cationic trypsinogen gene]. 1764 59