Sign in →

Test ID: HPPAN Hereditary Pancreatitis Panel

Useful For

Confirmation of suspected clinical diagnosis of familial or hereditary pancreatitis in patients with chronic pancreatitis

 

Identification of gene mutations contributing to pancreatitis in an individual or family

 

Identification of gene mutations to allow for predictive and diagnostic testing in family members

Method Name

Polymerase Chain Reaction (PCR) Amplification followed by DNA Sequencing/Multiplex Ligation-Dependent Probe Amplification (MLPA)

Reporting Name

Hereditary Pancreatitis Panel

Specimen Type

Varies


Specimen Required


Specimen Type: Whole blood

Container/Tube:

Preferred: Lavender top (EDTA) or yellow top (ACD)

Acceptable: Any anticoagulant

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send specimen in original tube.

Specimen Stability Information: Ambient (preferred)/Refrigerated

Additional Information: Specimen preferred to arrive within 96 hours of collection.


Specimen Minimum Volume

Blood: 1 mL

Specimen Stability Information

Specimen Type Temperature Time
Varies Ambient (preferred)
  Frozen 
  Refrigerated 

Clinical Information

Mutations in several genes, including PRSS1, CFTR, CTRC, and SPINK1 have demonstrated genetic susceptibility to chronic pancreatitis. Disease susceptibility may be monogenic, as is the case with PRSS1, digenic or multigenic, and multifactorial in which multiple genes and environmental factors play a role in disease expression.

                  

PRSS1:

Hereditary pancreatitis (HP) is defined as 2 or more individuals in a family affected with pancreatitis involving at least 2 generations. The most common monogenic cause of HP is the presence of a mutation in the cationic trypsinogen (PRSS1) gene. Mutations in the PRSS1 gene are inherited in an autosomal dominant manner. It has been reported that as many as 80% of patients with symptomatic hereditary pancreatitis have a causative PRSS1 mutation. HP cannot be clinically distinguished from other forms of pancreatitis. However, PRSS1 mutations are generally restricted to individuals with a family history of pancreatitis and are infrequently found in patients with alcohol-induced or tropical pancreatitis. Although several mutations have been identified, the R122H, N29I, and A16V mutations are the most common disease-causing mutations in PRSS1 associated with HP. Data suggests that the R122H mutation results in more severe disease and earlier onset of symptoms than the A16V mutation. 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%.  

 

SPINK1:

Biallelic mutations in the SPINK1 gene have been associated with increased susceptibility to chronic pancreatitis especially in families without PRSS1 mutations; however, it is unknown if biallelic mutations alone are sufficient to cause chronic pancreatitis. Additionally, heterozygous SPINK1 mutations appear to modify disease severity when observed in combination with mutations in other genes. Unlike PRSS1 mutations, SPINK1 mutations have been associated with alcohol-induced and tropical pancreatitis.

 

CFTR:

Pancreatitis is a known manifestation of an atypical CFTR-related disorder in which 2 mutations in the CFTR gene are identified. However, CFTR mutations can also co-occur with mutations in CTRC, SPINK1, or CASR to confer pancreatitis disease susceptibility. When observed in the context of a SPINK1 mutation, for example, heterozygous mutations in CFTR are associated with a 2- to 5-fold increased risk for pancreatitis as compared to the general population.

 

CTRC:

Mutations in CTRC have been observed in individuals with chronic pancreatitis in association with other risk factors such as mutations in CFTR or SPINK1 or specific environmental risk factors. Thus, chronic pancreatitis may be attributable to the presence of CTRC mutations in the context of other risk factors as opposed to CTRC mutations alone.

Reference Values

An interpretive report will be provided.

Interpretation

All detected alterations will be evaluated according to the American College of Medical Genetics and Genomics (AMCG) recommendations.(1) Variants will be classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

Clinical Reference

1. Richards S, Aziz N, Bale S, et al: Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015 May;17(5):405-424

2. Teich N, Mossner J: Hereditary chronic pancreatitis. Best Pract Res Clin Gastroenterol 2008;22(1):115-130

3. Solomon S, Whitcomb DC: Genetics of pancreatitis: an update for clinicians and genetic counselors. Curr Gastroenterol Rep 2012;14(2):112-117

4. 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

5. Pancreatitis Overview-GeneReviews-NCBI Bookshelf. Available at URL: http://www.ncbi.nlm.nih.gov/books/NBK190101/

Day(s) and Time(s) Performed

Performed weekly, varies

Analytic Time

14 days

CPT Code Information

81222-CFTR (cystic fibrosis transmembrane conductance regulator) (eg, cystic fibrosis) gene analysis; duplication/deletion variants

81223-CFTR (cystic fibrosis transmembrane conductance regulator) (eg, cystic fibrosis) gene analysis; full gene sequence

81404-PRSS1 (protease, serine, 1 [trypsin 1]) (eg, hereditary pancreatitis), full gene sequence 

81404-SPINK1 (serine peptidase inhibitor, Kazal type 1) (eg, hereditary pancreatitis), full gene sequence

81405-CTRC gene

LOINC Code Information

Test ID Test Order Name Order LOINC Value
HPPAN Hereditary Pancreatitis Panel In Process

 

Result ID Test Result Name Result LOINC Value
52581 Result Summary 50397-9
52582 Result In Process
52583 Interpretation 69047-9
52584 Additional Information 48767-8
52585 Specimen 31208-2
52586 Source 31208-2
52587 Released By No LOINC Needed

Test Classification

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.

Forms

1. Molecular Genetics: Congenital Inherited Diseases Patient Information (T521) in Special Instructions

2. New York Clients-Informed consent is required. Please document on the request form or electronic order that a copy is on file. An Informed Consent for Genetic Testing (T576) is available in Special Instructions.

Mayo Medical Laboratories | Genetics and Pharmacogenomics Catalog Additional Information:

mml-inherited-molecular