Category Archives: Pancreatic

Genetic testing is useful in the diagnosis of nonhereditary pancreatic conditions: CONCERNS AND OPPORTUNITIES Part 4

Future developments The major questions regarding genetic testing in the future will be who to test and when to test them. The technique is appropriate when the following conditions are met: 1. The patient will derive clinical benefit from the test results. 2. The test addresses the clinically relevant mutations. 3. The test is affordable, reliable, and easy to perform. 4. Insurance discrimination and other … Continue reading

Genetic testing is useful in the diagnosis of nonhereditary pancreatic conditions: CONCERNS AND OPPORTUNITIES Part 3

Interpretation of test results The results of genetic testing have implications for both the subject and his or her extended family. Roughly 80% of individuals with either the R122H or the N29I trypsinogen mutation will experience at least one episode of acute pancreatitis (ie, the disease penetrance is 80%). About one-half of clinically affected persons with either mutation will develop symptomatic chronic pancreatitis, and there … Continue reading

Genetic testing is useful in the diagnosis of nonhereditary pancreatic conditions: CONCERNS AND OPPORTUNITIES Part 2

Accuracy of testing Modern and properly applied genetic testing techniques yield positive and negative predictive values of almost 100% for identifying specific mutations. The pretest probability of a test for a PRSS1 mutation depends on several factors. The strongest predictors of a genetic basis for a case of pancreatitis include a typical family history (especially an autosomal dominant inheritance pattern) and an early age of … Continue reading

Genetic testing is useful in the diagnosis of nonhereditary pancreatic conditions: CONCERNS AND OPPORTUNITIES Part 1

Fears about genetic testing The decision about whether to proceed with genetic testing is often complex. Currently, the utility of this technique is limited by our incomplete understanding of the etiology of pancreatic disease and our inability to use genetic information to alter the clinical outcomes. Even though these factors will change in the future, the patients’ fears of genetic testing result in significant hesitation. … Continue reading

Genetic testing is useful in the diagnosis of nonhereditary pancreatic conditions: SPINK1/PSTI GENE MUTATIONS Part 2

Gene-gene interactions We have argued that SP1NK1 mutations act as disease promoters in that they lower the threshold for initiating pancreatitis or possibly worsen the severity of pancreatitis that is caused by other genetic or environmental factors. It has also been shown that the presence of PRSS1 and SP1NK1 mutations in the same person influences the phenotype. The author’s group and the Midwest Multicenter Pancreatic … Continue reading

Genetic testing is useful in the diagnosis of nonhereditary pancreatic conditions: SPINK1/PSTI GENE MUTATIONS Part 1

SPINK1 function PST1, which is also known by its UniGene name, SP1NK1 , is a 56-amino acid peptide that specifically inhibits trypsin by physically blocking the active site. SP1NK1 is synthesized by pancreatic acinar cells together with trypsinogen and is located in the same zymogen granules. In the mechanistic models of pancreatic acinar cell protection, SP1NK1 acts as the first line of defence against prematurely … Continue reading

Genetic testing is useful in the diagnosis of nonhereditary pancreatic conditions: CFTR GENE Part 2

Genetic testing CFTR is a large molecule with 1480 amino acids coded for by over 4400 nucleotides in 24 exons. Idiopathic chronic pancreatitis appears to be associated with some loss of CFTR function, which can be caused by many combinations of CFTR mutations. However, screening of the entire CFTR gene for mutations is difficult and very expensive, thereby limiting this approach to specialized research laboratories. … Continue reading

Genetic testing is useful in the diagnosis of nonhereditary pancreatic conditions: CFTR GENE Part 1

CFTR mutations causing cystic fibrosis The primary CFTR mutation-related disorder is cystic fibrosis (CF), which is one of the most common life-threatening autosomal recessive disorders in Caucasians. Major mutations in both alleles of the gene result in the commonly recognized clinical features of CF: abnormal sweat chloride concentrations, neonatal hypertrypsinogenemia, pancreatic pseudocysts, fibrosis (hence the term ‘cystic fibrosis’), chronic pancreatitis, and progressive pulmonary disease . Among CF … Continue reading

Genetic testing is useful in the diagnosis of nonhereditary pancreatic conditions: PRSS1 MUTATIONS Part 2

Genetic testing Genetic testing for hereditary pancreatitis has been available for research and clinical purposes for the past five years. The major issues surrounding genetic testing were recently reviewed. In general, the indications for clinical genetic testing vary widely according to the severity of the disease, the age of onset, the availability of surrogate markers and the possibility of an effective intervention. Patients are also … Continue reading

Genetic testing is useful in the diagnosis of nonhereditary pancreatic conditions: PRSS1 MUTATIONS Part 1

Cationic trypsinogen is among the most abundant molecules produced by pancreatic acinar cells. It plays a central role in hydrolyzing dietary proteins at lysine and arginine amino acid residues, and also in activating all other digestive proenzymes. Premature activation of trypsinogen within the pancreas leads to pancreatic autodigestion and is believed to be a key step in the pathogenesis of acute pancreatitis. Recurrent attacks of … Continue reading