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)

Cystic fibrosis (CF) is a genetic disease with multisystem involvement in which defective chloride transport across membranes causes dehydrated secretions. The protein encoded by the CF gene--the cystic fibrosis transmembrane conductance regulator (CFTR)--functions as a cyclic adenosine monophosphate-regulated chloride channel. The ability to detect CFTR mutations has led to the recognition of its association with a variety of conditions, including chronic bronchitis, sinusitis with nasal polyps, pancreatitis, and, in men, infertility. This article reviews the impact of CF on the pancreas, the role of the CFTR protein in pancreatic secretion, and some of the exciting research identifying mutations in the CFTR gene as a risk factor for idiopathic acute and chronic pancreatitis.
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PMID:Pancreatitis and cystic fibrosis gene mutations. 1050 35

Despite the recent development of medical imaging technology, chronic pancreatitis can only be diagnosed when the disease is fully established. This is due to the lack of specific and sensitive markers for this disease. The discovery of mutations in the cationic trypsinogen gene in patients with hereditary pancreatitis and a high incidence of mutations in the cystic fibrosis transmembrane conductance regulator gene in patients with chronic pancreatitis might be important clues to understanding the molecular mechanisms of this disease. The interaction between ethanol and ion channels might be the missing link between alcohol ingestion and chronic pancreatitis.
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PMID:Molecular understanding of chronic pancreatitis: a perspective on the future. 1052 91

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 (HP) is an autosomal dominant disease. Two heterozygous missense mutations, R122H (R117H) and N29I (N21I), in the cationic trypsinogen gene have been clearly associated with HP. The 'self-destruct' model proposed for the R122H mutation is discussed in connection with the existing theory of pancreatitis, and the basic biochemistry and physiology of trypsinogen, with particular reference to R122 as the primary autolysis site of the cationic trypsinogen. Two different genetic mechanisms are identified which cause the R122H mutation, and gene conversion is the likely cause of the N29I mutation. A unifying model, which highlights an indirect impairment on the R122 autolysis site is hypothesised for the N29I mutation. Possible predisposition to pancreatitis by additional DNA variants in the gene, such as the A16V signal peptide cleavage site mutation and the K23R activation peptide cleavage site mutation is suspected, but not proven. Evidence of genetic heterogeneity of HP is reviewed and cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations detected in HP families are re-evaluated. Finally, large scale association studies are expected to clarify the additional variants' role in pancreatitis and to identify new HP genes.
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PMID:Molecular basis of hereditary pancreatitis. 1090 45

Chronic pancreatitis is an inflammatory disease causing structural and progressive damage resulting in permanent deficit of both the exocrine and endocrine components. Although a few risk factors for the disease are known, of which the primary one is alcohol consumption, the actual mechanisms responsible for the initial steps and evolution of the disease are not. The discovery of mutations in the cationic trypsinogen gene in patients with hereditary pancreatitis and a high incidence of mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR) in patients with chronic pancreatitis might be important clues to understanding the molecular mechanisms of this disease.
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PMID:Genetics of chronic pancreatitis. 1098 79

Hereditary pancreatitis (HP) is clinically indistinguishable from pancreatitis with other causes. Patients with HP have an increased chance of developing pancreatitis. Mutations in the cationic trypsinogen gene appear to cause most HP, although there is evidence for mild genetic heterogeneity with defects in other genes. Trypsin stabilization and protection from autolysis appear to play a central role in the pathogenesis of pancreatitis. The role of mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) as well as the pancreatic secretory trypsin inhibitor (PSTI) in patients with pancreatitis is intriguing but as yet incompletely understood. Genetic testing may help to identify and manage patients with HP. Healthcare professionals should understand the elements necessary for obtaining informed consent for patients undergoing these tests, the limits in interpreting test results, and the psychosocial issues that may arise from genetic testing.
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PMID:Genetic testing in acute and chronic pancreatitis. 1127 78

There is increasing appreciation for the presence of diseases which do not fit the criteria for classic cystic fibrosis but are caused by dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR). This case describes a patient with documented CFTR dysfunction by nasal potential difference measurement who presents with chronic idiopathic pancreatitis, sinusitis, and allergic bronchopulmonary aspergillosis (ABPA), but not congenital bilateral absence of the vas deferens (CBAVD) or other classic symptoms of cystic fibrosis. This rare case demonstrates both the spectrum of disease which can be seen with CFTR dysfunction and the steps required to document CFTR involvement.
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PMID:The spectrum of CFTR-related disease. 1144 79

Pancreatitis-associated gene mutations have been reported in patients with hereditary pancreatitis and idiopathic pancreatitis in the Caucasian population and involve the cationic trypsinogen gene, the pancreatic secretory trypsin inhibitor gene and the cystic fibrosis transmembrane conductance regulator gene. In the Japanese population, mutational screening analyses of these genes have shown several mutations. The present study reviews previous reports from Japan in order to evaluate the racial specificity of pancreatitis-associated gene mutations.
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PMID:Hereditary pancreatitis in Japan: a review of pancreatitis-associated gene mutations. 1212 Feb 22

Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene are associated with different related disorders such as congenital bilateral absence of the vas deferens, chronic idiopathic pancreatitis, or disseminated bronchiectasis (DB). Many different disease-causing mutations are associated with DB, particularly the 5T allele (IVS 8 polyT tract), a variant of the splice acceptor site at the end of intron 8 that affects the efficiency with which the site is used. It therefore affects the accuracy of exon 9 splicing and hence expression of the functional CFTR protein. In this study we quantified transcripts from nasal biopsies of patients with DB compared to normal controls. We developed a real-time quantitative reverse transcription polymerase chain reaction assay (using the TaqMan system) to evaluate the relative amounts of accurately spliced transcript, and transcript lacking exon 9. Patients with the 5T allele had increased amounts of aberrant transcript: in genotypes 5T/7T, 7T/7T and 9T/7T, mean fractions of 38.4%, 3.5% and 0.6%, respectively, of transcripts had been spliced incorrectly. There was also some evidence that nasal biopsies can provide similar information on transcripts to bronchial biopsies. This functional test is of interest for monitoring the amount of CFTR transcript in different clinical situations or to monitor the effect of drugs on CFTR transcription.
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PMID:Quantification of CFTR splice variants in adults with disseminated bronchiectasis, using the TaqMan fluorogenic detection system. 1212 89

Cystic fibrosis is rare in the Asian population, and is often associated with consanguinity and rare genotypes. We report on a 23-year-old Asian man from a consanguineous pedigree referred to the regional cystic fibrosis unit after a diagnosis of congenital bilateral absence of the vas deferens during investigations for infertility. A detailed history revealed several previous episodes of acute pancreatitis. Full diagnostic appraisal showed homozygosity for a novel cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation, but normal sweat test and nasal potential difference studies. An endoscopic retrograde cholangiopancreatogram (ERCP) showed chronic pancreatitis with bulky side branches. The vas deferens and the pancreas appeared exquisitely sensitive to mild CFTR dysfunction. Patients with cystic fibrosis and unexplained upper abdominal pain should be screened for pancreatitis, and consideration should be given to screening patients with idiopathic pancreatitis for mutations in the CFTR gene.
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PMID:Cystic fibrosis presenting as acute pancreatitis and obstructive azoospermia in a young adult male with a novel mutation in the CFTR gene. 1242 49


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