Pancreatitis Testing

Pancreatitis is characterized by recurring inflammatory attacks that gradually cause irreversible damage to the pancreas and surrounding tissue.  Risk factors for pancreatitis range from environmental to genetic.   

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Pancreatitis is characterized by recurring inflammatory attacks that gradually cause irreversible damage to the pancreas and surrounding tissue.  Risk factors for pancreatitis range from environmental to genetic.   

Understanding a person’s genetic risk for pancreatitis can help alter lifestyle choices, plan appropriate management, and offer risk assessment in family members.  Ambry offers a range of testing options for analyzing the genetic risk for pancreatitis.

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.  Chronic pancreatitis (CP, recurrent episodes lasting longer than six months) is the most common presentation in familial and hereditary pancreatitis, but acute (sudden onset) and recurrent acute (more than one episode within six months), have also been associated with gene mutations.1  Functional impairment of the pancreas increases risks of diabetes and pancreatic cancer.1,2  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.3  Familial pancreatitis is defined as pancreatitis from any cause, which occurs in a family more frequently than would be expected by chance alone; its cause may be non-genetic or genetic.1  Hereditary pancreatitis is defined as either two or more individuals with pancreatitis in two or more generations of a family, or that 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.  Hereditary pancreatitis may also present as part of a rare genetic syndrome.  Symptoms of hereditary pancreatitis may begin as early as childhood, and is inherited in a number of ways, depending on the gene(s) involved.  

One common cause of hereditary pancreatitis involves mutations in the PRSS1 gene, and is inherited in an autosomal dominant pattern.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.1  Mutations in other genes, SPINK1 and CFTR, are also associated with susceptibility to pancreatitis, and are inherited in an autosomal recessive pattern.3  Another gene found to increase susceptibility to hereditary pancreatitis is CTRC; mutations in CTRC are inherited in either an autosomal recessive pattern, autosomal dominant, or in combination with mutations in other hereditary pancreatitis genes.    

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 

Ambry offers a variety of testing options for CP to suit several clinical needs:

  • Pancreatitis Panel includes full gene sequencing of PRSS1, SPINK1, and CFTR.
  • Pancreatitis+CFTR del/dup includes full gene sequencing of PRSS1, SPINK1, and CFTR, with CFTR deletion/duplication analysis.
  • Pancreatitis Panel+CTRC includes full gene sequencing of PRSS1, SPINK1, CFTR, and CTRC

Individual sequencing of PRSS1, SPINK1, CFTR, and CTRC, along with deletion/duplication analysis of the CFTR gene, is available.  Specific Site Analysis of mutations identified previously in a family member is also available.

Ambry’s in-house data for mutations found in patients with hereditary and idiopathic chronic pancreatitis are similar to other data recently published.3,5,6  In Ambry’s sample, 9% of patients had mutations in more than one gene; approximately 6% had mutations in PRSS1 only.  Though patients known to have cystic fibrosis were excluded, 11% had a form of non-classical CF confirmed by the presence of two CFTR mutations; an additional 21% had one CFTR mutation.  2-3% were found to have variants in the CTRC gene (unpublished data). 

Testing Benefits & Indication 

Genetic testing is useful for diagnostic confirmation in symptomatic individuals and for testing of at-risk asymptomatic family members.  Testing can help avoid repeated diagnostic tests and help guide recommendations for surveillance and reducing exposure to environmental risk factors (such as smoking and alcohol intake).  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
  • Unexplained chronic pancreatitis without a positive family history, after exclusion of other causes
  • 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 

CFTR: Exons 1 to 27 coding domains, plus at least 20 bases into the 5’- and 3’-ends of all introns, as well as at least 20 bases into the 5’- and 3’-untranslated regions (5’UTR and 3’UTR), are analyzed. This assay is also capable in assessing the poly-T tract within intron 8 and in identifying the c.1679+1634A>G (c.1811+1634A>G or c.1811+1.6kb) mutation in intron 12 and the c.3717+12191C>T (c.3849+10kbC>T) mutation in intron 22.  All 23 ACOG and ACMG recommended mutations are analyzed as well. Previously described mutations and novel variants are always reported. Polymorphisms and the poly T status will be reported upon request. PRSS1: Exons 1 to 5 coding domains, plus at least 20 bases into the 5' and 3' ends of all the introns, 5'- and 3'-untranslated regions (5'UTR and 3'UTR), are analyzed. SPINK1: Exons 1 to 4 coding domains, plus at least 20 bases into the 5' and 3' ends of all the introns, as well as at least 20 bases into the 5'- and 3'-untranslated regions (5'UTR and 3'UTR), are analyzed. CTRC: Exons 1-8 coding domains, plus at least 20 bases into the 5’ and 3’ ends of all the introns, as well as at least 20 bases into the 5’- and 3’-untranslated regions (5’UTR and 3’UTR), are analyzed. The following sites are used to search for previously described variants in the CFTR, PRSS1, SPINK1, and CTRC genes: HGMD and online search engines (i.e. PubMed). Toronto Sick Children's CF database and Leipzig Databases are also used to search for previously described CFTR and PRSS1/SPINK1 mutations and polymorphisms, respectively. Sequence analysis is based on the following NCBI reference sequences: CFTR-NM_000492.3, PRSS1-NM_002769.4, SPINK1-NM_003122.3, and CTRC-NM_007272.

Mutation Detection Rate 

About 48% of people with unexplained or hereditary CP with have a mutation in at least one of the four genes included in the Pancreatitis Panel+CTRC (clinical sensitivity).3  Sequence analysis detects approximately 99% of mutations in PRSS1, SPINK1 and CTRC, and detects 97-98% of mutations in CFTR.  Deletion/duplication analysis in addition to gene sequencing detects approximately 99% of CFTR mutations (analytic 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.

*Note for Blood Spots: blood spots are not accepted for PRSS1 analysis.  Blood Spots are accepted for CFTR, CTRC and SPINK1.

Turnaround Time 
TEST CODE Technique Days                    
8020 Pancreatitis Panel (CFTR, PRSS1, SPINK1)                                                         14-28
8040 Pancreatitis+CFTR del/dup (CFTR with deletion/duplication, PRSS1, SPINK1) 14-35
8022 Pancreatitis Panel+CTRC (CFTR, PRSS1, SPINK1, CTRC)                                     14-28
1100 PRSS1 Gene Sequence Analysis 14-28
1120 SPINK1 Gene Sequence Analysis               10-42
1660 CTRC Gene Sequence Analysis 14-21
1006 CFTR Gene Sequence Analysis, reflex to Deletion/Duplication                         5-13
  Specific Site Analysis, Any Gene 7-14

 

Genes 
References 
  1. LaRush J et al.  Pancreatitis Overview.  GeneReviews. 2014. Pagon RA, Adam MP, Ardiner HH 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.  [PMID 22314809]
  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.  [PMID 23951356]   
  4. Ellis I et al.  Genetic testing for hereditary pancreatitis: guidelines for indications, counselling, consent and privacy issues.  Pancreatology. 2001;1(5):405-15.  [PMID 12120217] 
  5. Keiles S, Kammesheidt A. Identification of CFTR, PRSS1, and SPINK1 mutations in 381 patients with pancreatitis. 2006. Pancreas. 33:221-227.  [PMID: 17003641]
  6. 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.  [PMID:22427236]