Hereditary Pancreatitis, Mutation Screen
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Hereditary pancreatitis (HP) is a rare autosomal dominant disorder, with approximately 80% penetrance. HP is characterized by early onset of acute pancreatitis during childhood or early adolescence. The acute pancreatitis in these patients generally progresses to chronic pancreatitis by adulthood and can eventually lead to both exocrine and endocrine pancreatic insufficiency. Patients with HP are also at an increased risk for developing pancreatic cancer. Studies have estimated the lifetime risk of developing pancreatic cancer to be as high as 40%.
HP cannot be clinically distinguished from other forms of pancreatitis. However, PRSS1 mutations are generally restricted to individuals with a family history of pancreatitis. PRSS1 mutations are infrequently found in patients with alcohol-induced and tropical pancreatitis.
The protease serine 1 or cationic trypsinogen (PRSS1) gene is located on chromosome 7. It has been reported that as many as 80% of patients with symptomatic hereditary pancreatitis have a causative PRSS1 mutation. Although several mutations have been identified, the Arg122His (R122H), Asn29Ile (N29I), and Ala16Val (A16V) mutations have been identified as the primary causative defects in HP. The phenotype of patients with these 3 mutations is quite similar, sharing many clinical features, though there are some differences. Data suggests that the R122H mutation results in more severe disease and earlier onset of symptoms, while the A16V mutation has reduced penetrance. Although these 3 alterations account for >90% of mutations detected in the cationic trypsinogen gene, the inability to identify mutations in approximately 20% of families with HP suggests the possible involvement of other loci or unidentified mutations in the cationic trypsinogen gene.
Confirming the diagnosis of hereditary pancreatitis (HP) in patients with chronic pancreatitis
Ruling out HP in patients with chronic pancreatitis
An interpretive report will be provided.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
A small percentage of individuals who are carriers or have a diagnosis of hereditary pancreatitis (HP) may have a mutation that is not identified by this method (eg, mutations in other exons, promoter mutations). The absence of a mutation(s), therefore, does not eliminate the possibility of positive carrier status or the diagnosis of HP. For carrier testing, it is important to first document the presence of a PRSS1 gene mutation in an affected family member.
In some cases, DNA alterations of undetermined significance may be identified.
Rare polymorphisms exist that could lead to false-negative or false-positive results. If results obtained do not match the clinical findings, additional testing should be considered.
A previous bone marrow transplant from an allogenic donor will interfere with testing. Call Mayo Medical Laboratories for instructions for testing patients who have received a bone marrow transplant.
Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in our interpretation of results may occur if information given is inaccurate or incomplete.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
An interpretive report will be provided.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Teich N, Mossner J: Hereditary chronic pancreatitis. Best Pract Res Clin Gastroenterol 2008;22(1):115-30
2. Howes N, Greenhalf W, Stocken DD, Neoptolemos JP: Cationic trypsinogen mutations and pancreatitis. Clin Lab Med 2005;25:39-59
3. Ellis I: Genetic counseling for hereditary pancreatitis-the role of molecular genetics testing for the cationic trypsinogen gene, cystic fibrosis and serine protease inhibitor Kazal type 1. Gastroenterol Clin North Am 2004;33:839-854