Pancreatitis Testing

Pancreatitis is characterized by recurring inflammatory attacks that gradually cause irreversible damage to the pancreas and surrounding tissue. Risk factors range from environmental to genetic. Understanding genetic risk for pancreatitis can help alter lifestyle choices, plan appropriate management, and offer risk assessment in family members.

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Pancreatitis is characterized by recurring inflammatory attacks that gradually cause irreversible damage to the pancreas and surrounding tissue. Risk factors range from environmental to genetic. Understanding genetic risk for pancreatitis can help alter lifestyle choices, plan appropriate management, and offer risk assessment in family members.

Disease Name 
Pancreatitis
Familial pancreatitis
Hereditary pancreatitis
Idiopathic sporadic pancreatitis
Recurrent idiopathic pancreatitis
Disease Information 

Pancreatitis is an inflammation of the pancreas, which can progress to irreversible damage to the pancreas and surrounding tissue.  Attacks may be sudden or recurrent.  The three types of pancreatitis are:1, 2

The three types of pancreatitis are:1,2
   
Acute pancreatitis  Sudden onset
Recurrent acute pancreatitis  More than one episode in six months
Chronic pancreatitis (CP) Recurrent episodes lasting longer than six months

 

Alcoholism and other environmental factors are the primary cause of CP, but in 20% of cases, no environmental cause is found.  Of these idiopathic cases of CP, genetics may play a major role: In addition, while CP is the most common presentation in familial and hereditary pancreatitis, acute and recurrent acute pancreatitis have also been associated with gene mutations.1  Functional impairment of the pancreas increases risks of diabetes and pancreatic cancer.

 
   
Familial pancreatitis
  • Pancreatitis that occurs in a family more frequently than would be expected by chance alone
  • May be non-genetic or genetic.1
Hereditary pancreatitis
  • 2 or more individuals with pancreatitis in 2 or more generations of a family 
    OR
  • Pancreatitis associated with a germline disease-causing gene mutation.1  

 

Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the CFTR gene, and some forms are known to cause pancreatitis.  Symptoms of hereditary pancreatitis may begin as early as childhood and may present as an isolated symptom or as part of a rare genetic syndrome.  Hereditary pancreatitis can be inherited in a number of ways, depending on the gene(s) involved.  

One common cause of hereditary pancreatitis involves mutations in the PRSS1 gene.1,3  PRSS1 codes for an enzyme called cationic trypsinogen, which aids in digestion.  Mutations in PRSS1 are found in at least 60% of families with hereditary CP and are inherited in an autosomal dominant fashion.1   Mutations in SPINK1, CFTR, and CTRC, are also associated with susceptibility to pancreatitis though penetrance and expressivity are highly variable.5

Monoallelic mutations in these genes may result in a pancreatitis phenotype on their own or may contribute to and modify the phenotype when inherited in combination with pathogenic mutations in other genes.3 Biallelic mutations within the same gene may result in a more severe pancreatitis phenotype.  

Understanding one’s risk of developing CP can lead to lifestyle choices that can dramatically reduce the risk of developing CP and associated long term health problems, including diabetes and pancreatic cancer.1,2  Abstaining from or reducing alcohol consumption, as well as smoking, has been shown to reduce the risk of long-term complications in people with a risk of CP.  In addition, adoption of a low-fat diet can also help to reduce the risks of associated health problems.1,4 

We offer comprehensive testing for CP featuring next generation sequencing (NGS):

  • Pancreatitis Panel includes NGS of PRSS1, SPINK1, CTRC, and CFTR

Individual sequencing of PRSS1, SPINK1, CTRC, and CFTR is available.  Specific Site Analysis of mutations identified previously in a family member is also available.

Testing Benefits & Indication 

Genetic testing is useful for:

  • Diagnostic confirmation in symptomatic individuals
  • Testing of at-risk asymptomatic family members.
  • Helping to avoid repeated diagnostic tests
  • Guiding recommendations for surveillance and reducing exposure to environmental risk factors (such as smoking and alcohol intake)

The American College of Gastroenterology guidelines state that genetic testing should especially be considered in patients <30 years old.6  Genetic testing may be considered for any of the following:4

  • Recurrent unexplained attacks of acute pancreatitis and a positive family history
  • Unexplained chronic pancreatitis and a positive family history
  • Hereditary hyperthyroidism and autoimmune pancreatitis
  • Unexplained acute pancreatitis episode in children
  • At-risk family members, including children in families with early onset symptoms
Test Description 

Our Pancreatitis panel includes next generation sequencing (NGS) of PRSS1, SPINK1, CTRC, and CFTR.  Genomic deoxyribonucleic acid (gDNA) is isolated from the patient’s specimen using a standardized kit and quantified. Sequence enrichment of the targeted coding exons and adjacent intronic nucleotides is carried out by a bait-capture methodology using long biotinylated oligonucleotide probes, followed by polymerase chain reaction (PCR) and next generation sequencing (NGS). Additional Sanger sequencing is performed for any regions missing, or with insufficient read depth coverage for reliable heterozygous variant detection. Suspect variant calls other than "likely benign" or "benign" are verified by Sanger sequencing. This test targets detection of DNA sequence mutations in all coding domains, and well into the 5’ and 3’ ends of all the introns and untranslated regions.

 

Mutation Detection Rate 

~48% of people with unexplained or hereditary CP will have a mutation in at least one of the four genes included (clinical sensitivity). Our pancreatitis testing can detect >99.9% of described mutations in the included genes, when present (analytical sensitivity). 

Specimen Requirements 

Complete specimen requirements are available here or by downloading the PDF found above in the quick links section at the top of this page.

Turnaround Time 
TEST CODE TECHNIQUE TURNAROUND TIME (days)
8022 Pancreatitis Panel (CFTR, PRSS1, SPINK1, CTRC) 14-28
1100 PRSS1 Gene Sequence Analysis 14-28
1120 SPINK1 Gene Sequence Analysis   14-28
1660 CTRC Gene Sequence Analysis 14-28
1006 CFTR Gene Sequence Analysis, reflex to Deletion/Duplication 5-13

 

Genes 
PRSS1
SPINK1
CFTR
CTRC
Techniques 
References 
1. LaRush J, et al.  Pancreatitis Overview.  GeneReviews. March 13, 2014. Pagon RA, et al., editors. Seattle (WA): University of Washington, Seattle; 1993-2014.

2. Solomon S and Whitcomb DC.  Genetics of pancreatitis: an update for clinicians and genetic counselors.  Curr Gastroenterol Rep. 2012 Apr;14(2):112-7. 

3. Mason E, et al.  A conservative assessment of the major genetic causes of idiopathic chronic pancreatitis: Data from a comprehensive analysis of PRSS1, SPINK1, CTRC and CFTR genes in 253 young French patients.  PLoS One. 2013 Aug 8;8(8):e73522. 

4. Ellis I, et al.  Genetic testing for hereditary pancreatitis: guidelines for indications, counselling, consent and privacy issues.  Pancreatology. 2001;1(5):405-15.

5. Rosendahl J, et al.   CFTR, SPINK1, CTRC and PRSS1 variants in chronic pancreatitis: is the role of mutated CFTR overestimated?  Gut. 2013 Apr;62(4):582-92.

6. Tenner S, et al.  American College of Gastroenterology guideline: management of acute pancreatitis.  Am J Gastroenterol. 2013 Sep;108(9):1400-15.