Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030305 (pancreatitis)
 16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The etiology of nonalcoholic chronic pancreatitis, occurring in tropical regions, is unknown. Although environmental factors may play a role in its pathogenesis, a specific genetic predisposition may be necessary. The genetic mutation responsible for hereditary pancreatitis was described recently. Unlike in patients with hereditary pancreatitis, we found a lack of the R117H mutation in the cationic trypsinogen gene in all patients with tropical pancreatitis from Bangladesh.
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PMID:Lack of R117H mutation in the cationic trypsinogen gene in patients with tropical pancreatitis from Bangladesh. 978 42

Cystic fibrosis is by far the commonest cause of chronic pancreatitis in children, but pancreatitis itself is only rarely its presenting feature. In this paper an hypothesis for the development of the pancreatic lesions is presented. Impaired activation of pancreatic proteases in the small intestine is perceived as the pivotal problem that leads to continual feedback release of cholecystokinin, thus, in effect, causing a chronic hyperstimulation pancreatitis with intra-acinar activation of zymogens and, when bicarbonate secretion falls, precipitation of 'Reg' and other proteins in the duct system. This position contrasts with that in hereditary pancreatitis in which a mutation in the cationic trypsinogen gene leads to a form of trypsin that resists degradation by mesotrypsin and enzyme Y. A survey of the literature suggests that oxidant stress is a plausible contributor to pancreatic injury in both these diseases and in several other conditions linked with childhood pancreatitis.
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PMID:Paediatric and hereditary aspects of chronic pancreatitis. 983 35

Hereditary pancreatitis (HP) is the second most common cause of chronic childhood pancreatitis in the United States. Mutations in the cationic trypsinogen gene on chromosome 7 are known to cause HP. We identified four families in West Virginia with symptoms consistent with HP. To determine whether members of these families had defects in the trypsinogen gene, we tested for linkage between the HP gene and simple tandem repeat markers on chromosome 7q and screened for a specific mutation in the cationic trypsinogen gene. Two-point linkage analysis indicated that the disease gene is closely linked to three 7q markers (D7S661, D7S2511, and D7S1805). Restriction fragment length polymorphism analysis showed that all clinically affected members and nonpenetrant carriers from the four families carried a G to A mutation in the third exon of the trypsinogen gene. These findings indicate that this mutation is the cause of HP in the families in our study. The observation that most individuals who carry the mutation have symptoms of HP is consistent with the high but incomplete penetrance of the trait. The presence of a single mutation and a common linked haplotype indicates that the defective allele arose in an ancestor common to all four families.
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PMID:Identification of a hereditary pancreatitis mutation in four West Virginia families. 985 29

Hereditary pancreatitis (HP) is a rare inherited disorder, characterised by recurrent episodes of pancreatitis often beginning in early childhood. The mode of inheritance suggests an autosomal dominant trait with incomplete penetrance. The gene, or at least one of the genes, responsible for hereditary pancreatitis has been mapped to the long arm of chromosome 7 and a missense mutation, an arginine to histidine substitution at residue 117 in the trypsinogen cationic gene (try4) has been shown to segregate with the HP phenotype. The aim of this work was to investigate the molecular basis of hereditary pancreatitis. This study was performed on 14 HP families. The five exons of the trypsinogen cationic gene were studied using a specific gene amplification assay combined with denaturing gradient gel electrophoresis (DGGE). The present paper describes three novel mutations, namely K23R and N29I and a deletion -28delTCC in the promoter region. We also found a polymorphism in exon 4, D162D. In eight of these families we found a mutation which segregates with the disease. A segregation analysis using microsatellite markers carried out on the other families suggests genetic heterogeneity in at least one of them. Our findings confirm the implication of the cationic trypsinogen gene in HP and highlight allelic diversity associated with this phenotype. We also show that the pattern of inheritance of HP is probably complex and that other genes may be involved in this genetic disease.
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PMID:Mutations in the cationic trypsinogen gene and evidence for genetic heterogeneity in hereditary pancreatitis. 1020 51

Hereditary pancreatitis is a rare form of chronic recurrent pancreatitis. A family, in which 11 members had chronic pancreatitis, five had diabetes, and two had pancreatic cancer, was studied, and hereditary pancreatitis was diagnosed in all patients by demonstrating the mutation in exon 3 of the cationic trypsinogen gene (R117H). The clinical implications of genotypic analysis in hereditary pancreatitis are discussed.
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PMID:Hereditary pancreatitis and mutation of the trypsinogen gene. 1020 58

Nine out of 48 (19%) patients referred to a pancreatic clinic with a presumed diagnosis of idiopathic chronic pancreatitis have been shown to have mutations in the cationic trypsinogen gene (PRSSI), consistent with a previously unsuspected diagnosis of hereditary pancreatitis.
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PMID:Mutations of the cationic trypsinogen gene in patients with chronic pancreatitis. 1052 Jun 63

Few risk factors for pancreatic cancer have emerged except for chronic pancreatitis. Recently, hereditary pancreatitis was estimated to carry a standardized incidence ratio of 53, a risk about 25 times higher than smoking. A review of the ongoing hereditary pancreatitis study of the Midwest Multicenter Pancreatic Study Group suggests that the risk of pancreatic cancer is related to long-standing pancreatitis rather than to the cationic trypsinogen mutations. No recommendations can be made on screening patients with hereditary pancreatitis for pancreatic cancer at this time. However, prospective data, serum, and pancreatic juice should be collected and banked on consenting patients at risk as part of prospective, multicenter trials so that evidence-based recommendations for hereditary pancreatitis and other types of chronic pancreatitis can be made in the future.
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PMID:Hereditary pancreatitis and pancreatic carcinoma. 1041 65

Hereditary Pancreatitis (HP), is an autosomal dominant trait, which presents with recurrent attacks of abdominal pain, and is the most common cause of chronic relapsing pancreatitis in children. In addition to recurring episodes of intense epigastric pain, patients have nausea, vomiting, and anorexia, and typically show elevated serum amylase levels during the acute episode that can rapidly decline in convalescence. Complications of long-standing disease include features of chronic pancreatitis, such as pancreatic pseudo-cyst, exocrine and endocrine failure, parenchymal calcification, and pancreatic cancer. A large family from Virginia, which was originally studied by Katwinkle and Lapey in 1973, was re-ascertained through a new proband. Linkage studies in this family mapped the gene to the 7q35 region, with similar results being reported simultaneously by two other groups. A pathogenic G to A transition mutation in exon 3 of the cationic trypsinogen (CT) gene, which had previously been mapped to this region, was found both in our family as well as other families from North America. Many other conditions can produce abdominal symptoms that are often mis-attributed to the disease in HP families. An affected member of our family in whom the mutation was confirmed by direct sequencing of exon 3 of the cationic trypsinogen gene requested diagnostic testing on his 4-year-old son because of onset of severe abdominal pain and vomiting. Screening for the mutation in this child did not reveal the pathogenic G to A change. These results prevented unnecessary invasive diagnostic procedures and treatment in this child. The pre-symptomatic testing of high risk individuals could, thus, have a significant impact on the well being of both affected and normal family members.
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PMID:Implications of molecular diagnostic testing in families with hereditary pancreatitis. 1046 47

The pancreatitis-associated protein (PAP) was investigated in patients with hereditary and chronic alcoholic pancreatitis. Blood levels of pancreatic enzymes and PAP were measured in nine families with hereditary pancreatitis; in three of them, the mutation N21I, and in six, the R117H variant of the cationic trypsinogen were present. In all family members, similar to controls, only normal values of the PAP were found. There was no evidence for polymorphism of the PAP gene in patients with hereditary or alcoholic pancreatitis. Immunohistochemically PAP was detected in the apical parts of the acinar cells but not in ducts, interstitial tissue, islets, or blood vessels. Intensity of PAP labeling was directly related to the deterioration of the acinar units, and its concentration was inversely related to chymotrypsinogen immunoreactivity in the same tissue. Similar immunohistochemical findings were present in chronic alcoholic and hereditary pancreatitis. We conclude that there is a lack of PAP polymorphism in hereditary and alcoholic pancreatitis and that expression of the PAP in both groups of patients is related to the degree of cellular damage of the pancreas.
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PMID:The pancreatitis-associated protein in hereditary and chronic alcoholic pancreatitis. 1050 55

Mutations Arg117-->His and Asn21-->Ile of the human cationic trypsinogen have been recently identified in patients affected by hereditary pancreatitis (HP). The Arg117-->His substitution is believed to cause pancreatitis by eliminating an essential autolytic cleavage site in trypsin, thereby rendering the protease resistant to inactivation through autolysis. Here we demonstrate that the Arg117-->His mutation also significantly inhibits autocatalytic trypsinogen breakdown under Ca(2+)-free conditions and stabilizes the zymogen form of rat trypsin. Taken together with recent findings demonstrating that the Asn21-->Ile mutation stabilizes rat trypsinogen against autoactivation and consequent autocatalytic degradation, the observations suggest a unifying molecular pathomechanism for HP in which zymogen stabilization plays a central role.
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PMID:Trypsinogen stabilization by mutation Arg117-->His: a unifying pathomechanism for hereditary pancreatitis? 1052 93


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