Hereditary Pancreatitis Mutation Panel

Background

Hereditary pancreatitis (HP) is a rare, early-onset genetic disorder characterized by epigastric pain and often more serious complications. An Arg - His substitution at residue 122 in exon 3 of the cationic trypsinogen gene (PRSS1) is associated with the HP phenotype. Further mutations identified in exon 2 of PRSS1, N29I, and A16V along with the R122H mutation in exon 3 allow for the detection of 90 - 95% of mutations causing hereditary pancreatitis. All mutations have been shown to exhibit an autosomal dominant pattern of inheritance of incomplete penetrance (80%). These mutations permit uncontrolled trypsin activity and therefore autodigestion of the pancreas. Recurrent attacks of acute pancreatitis often lead to complications of chronic pancreatitis including failure of exocrine digestive functions, diabetes mellitus, pseudocysts, and increased risk of pancreatic cancer. Individuals carrying these mutated genes can be identified before pancreatitis begins, and may aid in the design of strategies for preventing or controlling the development of the clinical manifestations of the disease.

OMIM: 276000

Clinical Utility

Direct detection of the hereditary pancreatitis mutations is determined by separate DNA-based polymerase chain reaction (PCR) assays followed by restriction endonuclease digestion (RE digest). Amplification products that encompass the variants contain unique restriction sites at the mutation loci. The alteration of restriction site generates digestion products which are different from the wild type pattern.

Methodology

PCR amplification and Sanger sequencing of regions with known hotspots.

Loci Tested

Specimen Requirements

Peripheral blood collected in EDTA (purple top) is preferred, 3-10mL.

Turnaround Time

Within 1-3 weeks of receipt

CPT

81401

Shipment Must Include

Specimen
Requisition form
Patient pathology report

References

  1. Whitcomb, D.C. et al., Hereditary pancreatitis is caused by a mutation in the cationic trypsinogen gene, Nature Genetics 14: 141-145, 1996.
  2. Gorry, M.C. et al., Mutations in the cationic trypsinogen gene are associated with recurrent acute and chronic pancreatitis, Gastroenterology 113: 1063-1068, 1997.
  3. Ferec, C. et al., Mutations in the cationic trypsinogen gene and evidence for genetic heterogeneity in hereditary pancreatitis, J. Med. Genet. 36: 228-232, 1999.