Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0000737 (abdominal pain)
 31,184 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hereditary pancreatitis is an autosomal dominant disorder with incomplete penetrance. It is characterised by recurring episodes of severe abdominal pain and often presents in childhood. Recently, a mutation in the cationic trypsinogen gene was identified in this disease. Previously, only one mutation at residue 117 of the trypsinogen gene has been found in the five separate hereditary pancreatitis families, four from the USA and one from Italy. Alteration of the Arg117 site is believed to disrupt a fail-safe mechanism for the inactivation of trypsin, leading to autodigestion of the pancreas under certain conditions. Molecular analysis of the trypsinogen gene was carried out on a hereditary pancreatitis family from the UK. The same G to A mutation at residue 117 was identified in this family, suggesting that this is a common mutation in hereditary pancreatitis.
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PMID:Evidence for a common mutation in hereditary pancreatitis. 971 98

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

Hereditary pancreatitis (HP) is an autosomal dominant disorder characterized by recurrent acute attacks of severe abdominal pain with an onset in early childhood. Many HP patients progress to complicated chronic pancreatitis and/or pancreatic cancer. Initially, a single mutation R117H in the cationic trypsinogen gene was detected in all affected members of five unrelated HP families. Further studies identified a second mutation (N21L) in two HP families without the R117H mutation. Before the association between cationic trypsinogen and HP was found, we detected a cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation (L327R) in all affected individuals of a family with HP. We therefore performed a mutational analysis for R117H and N21L in cationic trypsinogen in this and three additional unrelated families with HP. The R117H mutation was detected in all 9 affected members of three HP families and in 3 asymptomatic but at-risk relatives. However, neither the R117H nor the N21L mutation in the cationic trypsinogen were found in the HP family with the L327R alteration in CFTR. The L327R allele segregates with the disease within this HP family and was not detected on 360 unrelated Caucasian non-CF chromosomes. Although close to 800 different mutations have been detected in the CF gene of cystic fibrosis patients, L327R is a new alteration, not yet reported in connection with CF. The results of this study indicate that the CFTR gene may play a role in the etiology of minority of cases with HP and suggest that hereditary pancreatitis is genetically heterogeneous disease.
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PMID:Evidence that hereditary pancreatitis is genetically heterogeneous disorder. 1065 40

Hereditary pancreatitis is an autosomal dominant form of chronic pancreatitis. It presents with recurrent attacks of acute pancreatitis, usually starting in early childhood. The attacks may vary from mild abdominal pain to pancreatic necrosis, splenic vein thrombosis, pseudocysts and death. Ultimately chronic pancreatitis ensues with unrelenting pain, calcifications, endocrine and exocrine dysfunction. The penetrance is estimated at 80%. With the use of genetic linkage analysis the gene for hereditary pancreatitis was placed on the long arm of chromosome 7 (7q35). Mutational analysis identified cationic trypsinogen as the disease gene. Cationic trypsinogen mutations are thought to result in resistance of this molecule to autolysis.
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PMID:[From gene to disease; hereditary pancreatitis]. 1114 96

Inflammatory disease of the pancreas falls into two major classifications: acute and chronic. Acute pancreatitis is a reversible process, whereas chronic pancreatitis produces irreversible changes in the architecture and function of the pancreas. The recent finding that mutations in the gene encoding cationic trypsinogen are associated with hereditary pancreatitis, the identification of genes that increase the risk for developing chronic pancreatitis, and advances in cell biology have contributed greatly to our understanding of the molecular mechanisms leading to pancreatitis. Although pancreatitis is less common in children than in adults, it still occurs with regularity and should be considered in any child with acute or chronic abdominal pain. The major difference between pancreatitis in children and adults lies in the etiologies and outcome of acute pancreatitis and in the etiology of chronic pancreatitis. The treatment of acute and chronic pancreatitis is similar at all ages.
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PMID:Pancreatitis in childhood. 1512 92

Hereditary chronic pancreatitis (HCP) is a very rare form of early onset chronic pancreatitis. With the exception of the young age at diagnosis and a slower progression, the clinical course, morphological features and laboratory findings of HCP do not differ from those of patients with alcoholic chronic pancreatitis. As well, diagnostic criteria and treatment of HCP resemble that of chronic pancreatitis of other causes. The clinical presentation is highly variable and includes chronic abdominal pain, impairment of endocrine and exocrine pancreatic function, nausea and vomiting, maldigestion, diabetes, pseudocysts, bile duct and duodenal obstruction, and rarely pancreatic cancer. Fortunately, most patients have a mild disease. Mutations in the PRSS1 gene, encoding cationic trypsinogen, play a causative role in chronic pancreatitis. It has been shown that the PRSS1 mutations increase autocatalytic conversion of trypsinogen to active trypsin, and thus probably cause premature, intrapancreatic trypsinogen activation disturbing the intrapancreatic balance of proteases and their inhibitors. Other genes, such as the anionic trypsinogen (PRSS2), the serine protease inhibitor, Kazal type 1 (SPINK1) and the cystic fibrosis transmembrane conductance regulator (CFTR) have been found to be associated with chronic pancreatitis (idiopathic and hereditary) as well. Genetic testing should only be performed in carefully selected patients by direct DNA sequencing and antenatal diagnosis should not be encouraged. Treatment focuses on enzyme and nutritional supplementation, pain management, pancreatic diabetes, and local organ complications, such as pseudocysts, bile duct or duodenal obstruction. The disease course and prognosis of patients with HCP is unpredictable. Pancreatic cancer risk is elevated. Therefore, HCP patients should strongly avoid environmental risk factors for pancreatic cancer.
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PMID:Hereditary chronic pancreatitis. 1720 47

Hereditary chronic pancreatitis (HCP) is a very rare form of early-onset chronic pancreatitis. Apart from young age at diagnosis and a slower progression, the clinical course, morphological features and laboratory findings of HCP do not differ from those of patients with alcoholic chronic pancreatitis. Diagnostic criteria and treatment of HCP also resemble those of chronic pancreatitis of other causes. The clinical presentation is highly variable and includes chronic abdominal pain, impairment of endocrine and exocrine pancreatic function, nausea and vomiting, maldigestion, diabetes, pseudocysts, bile-duct and duodenal obstruction, and rarely pancreatic cancer. Fortunately, the disease is mild in most patients. Mutations in the PRSS1 gene, encoding cationic trypsinogen, play a causative role in chronic pancreatitis. It has been shown that the PRSS1 mutations increase autocatalytic conversion of trypsinogen to active trypsin, and thus probably cause premature, intrapancreatic trypsinogen activation, disturbing the intrapancreatic balance of proteases and their inhibitors. Other genes--such as the anionic trypsinogen (PRSS2), the serine protease inhibitor Kazal type 1 (SPINK1), and the cystic fibrosis transmembrane conductance regulator (CFTR)--have also been found to be associated with chronic pancreatitis (idiopathic and hereditary). Genetic testing should only be performed in carefully selected patients by direct DNA sequencing, and antenatal diagnosis should not be encouraged. Treatment focuses on enzyme and nutritional supplementation, pain management, pancreatic diabetes, and local organ complications such as pseudocysts and bile-duct or duodenal obstruction. The disease course and prognosis of patients with HCP is unpredictable. The risk of pancreatic cancer is elevated. Therefore, HCP patients should strongly avoid environmental risk factors for pancreatic cancer.
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PMID:Hereditary chronic pancreatitis. 1820 17

Hereditary pancreatitis is an autosomal dominant disorder with 80% penetrance and variable expressivity. The vast majority of cases have been linked to mutations within the cationic trypsinogen gene, also referred to as serine protease 1 (PRSS1). Other than inheritance, PRSS1 pancreatitis has been considered clinically and pathologically indistinguishable from other etiologies of chronic pancreatitis. However, to date, the histologic findings of PRSS1 pancreatitis have not been well described. We, therefore, collected pancreatic specimens from 10 PRSS1 patients of various ages and examined their clinicopathologic features. Patients at the time of resection ranged in age from 9 to 66 years (median, 29 y), with a slight female predominance (60%). All patients reported a history of intermittent abdominal pain, with an age of onset ranging from infancy to 21 years of age. Examination of the gross and microscopic findings suggested a sequential pattern of changes with increasing patient age. In pediatric patients (n=4), although in most cases the pancreas was grossly normal, there was microscopic variation in lobular size and shape. Although the central portions of the pancreas displayed parenchymal loss accompanied by loose perilobular and interlobular fibrosis, the periphery was remarkable for replacement by mature adipose tissue. These changes were more developed in younger adults (n=2), in whom fatty replacement seemed to extend from the periphery to the central portions of the pancreas. With older patients (n=4), the pancreas showed marked atrophy and extensive replacement by mature adipose tissue with scattered islets of Langerhans and rare acinar epithelium concentrated near the main pancreatic duct. In summary, PRSS1 hereditary pancreatitis is characterized by progressive lipomatous atrophy of the pancreas.
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PMID:The histopathology of PRSS1 hereditary pancreatitis. 2452 5

Hereditary pancreatitis (HP) is an autosomal dominant disorder characterized by recurrent acute attacks of severe abdominal pain with an onset in early childhood. Many HP patients progress to complicated chronic pancreatitis and/or pancreatic cancer. Initially, a single mutation R117H in the cationic trypsinogen gene was detected in all affected members of five unrelated HP families. Further studies identified a second mutation (N21L) in two HP families without the R117H mutation. Before the association between cationic trypsinogen and HP was found, we detected a cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation (L327R) in all affected individuals of a family with HP. We therefore performed a mutational analysis for R117H and N21L in cationic trypsinogen in this and three additional unrelated families with HP. The R117H mutation was detected in all 9 affected members of three HP families and in 3 asymptomatic but at-risk relatives. However, neither the R117H nor the N21L mutation in the cationic trypsinogen were found in the HP family with the L327R alteration in CFTR. The L327R allele segregates with the disease within this HP family and was not detected on 360 unrelated Caucasian non-CF chromosomes. Although close to 800 different mutations have been detected in the CF gene of cystic fibrosis patients, L327R is a new alteration, not yet reported in connection with CF. The results of this study indicate that the CFTR gene may play a role in the etiology of minority of cases with HP and suggest that hereditary pancreatitis is genetically heterogeneous disease.
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PMID:Evidence that hereditary pancreatitis is genetically heterogeneous disorder. 2817 71