Chronic Hereditary Pancreatitis via the PRSS1 Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
8631 PRSS1 81404 81404,81479 $990 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8631PRSS181404 81404(x1), 81479(x1) $990 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information. If the Sanger option is selected, CNV detection may be ordered through Test #600.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing backbone).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing backbone).

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

Turnaround Time

18 days on average for standard orders or 13 days on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Chansonette Badduke, PhD

Clinical Features and Genetics

Clinical Features

Pancreatitis is characterized by recurrent episodes of inflammation of the pancreas in both adults and children (Chen and Ferec 2009). Symptoms usually begin in late childhood with an episode of acute pancreatitis and include severe upper abdominal burning pain radiating to the back, nausea, and vomiting that is worsened with eating (acute pancreatitis). Recurrent acute pancreatitis leads to chronic pancreatitis due to persistent inflammation. Chronic pancreatitis usually develops by early adulthood in affected individuals. Symptoms include occasional or frequent abdominal pain of varying severity, flatulence, and bloating. Unexplained weight loss may occur from a lack of pancreatic enzymes hindering digestion (Rebours et al. 2012). Episodes of pancreatitis can lead to permanent tissue damage and loss of pancreatic function. Chronic pancreatitis increases the risk for diabetes and pancreatic cancer, more so with smoking and use of alcohol (Yadav and Whitcomb 2010). Causative mutations in several genes have been identified in pancreatitis (Joergensen et al. 2010).

Genetics

Hereditary chronic pancreatitis (HP) due to mutations in the PRSS1 gene is inherited in an autosomal dominant mode with variable expressivity and clinical course. Mutations in the CFTR, SPINK1, and CTRC genes have also been shown to be causative for pancreatitis with lower penetrance when inherited in an autosomal recessive manner (Joergensen et al. 2010; Audrezet et al. 2002; Keiles and Kammesheidt 2006). Gain of function mutations allowing trypsinogen to become activated to trypsin in the pancreas, instead of the duodenum, are the major causative variants found with the cationic trypsinogen (PRSS1) gene. The c.365G>A (p.Arg122His) and c.86A>T (p.Asn29Ile) are most commonly found with these patients having 80% penetrance for HP. De novo mutations may be found in as high as 35% of patients with HP. Loss of function mutations in the PRSS1 gene have been found to be protective for HP (Chen and Férec 2009). Gross duplications of the PRSS1 gene have been described as a causative mechanism for disease (Le Maréchal et al. 2006). The PRSS1 gene encodes the protein trypsinogen, a peptidase produced in the pancreas that becomes activated after released into the duodenum to aid in digestion.

Clinical Sensitivity - Sequencing with CNV PGxome

The p.R122H mutation in exon 3 of PRSS1 is the most common alteration identified in individuals with PRSS1-associated HP. Our full gene sequencing test is expected to detect >98% of PRSS1 causative mutations.

Testing Strategy

This test provides full coverage of all coding exons of the PRSS1 gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

Indications for Test

Individuals with the following criteria should consider testing for mutations in PRSS1 (Ellis et al. 2001): 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 such as hyperlipidaemia type I, familiar hypercalciuric hypercalcemia (FBH), hereditary hyperthyroidism and autoimmune pancreatitis and unexplained pancreatitis episodes in children.

Gene

Official Gene Symbol OMIM ID
PRSS1 276000
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Pancreatitis, Chronic AD 167800

Related Test

Name
Chronic Pancreatitis Panel

Citations

  • Audrezet M-P, Chen J-M, Marechal C Le, Ruszniewski P, Robaszkiewicz M, Raguenes O, Quere I, Scotet V, Ferec C. 2002. Determination of the relative contribution of three genes–the cystic fibrosis transmembrane conductance regulator gene, the cationic trypsinogen gene, and the pancreatic secretory trypsin inhibitor gene–to the etiology of idiopathic chronic pancreatitis. European Journal of Human Genetics 10: 100-106. PubMed ID: 11938439
  • Chen J-M, Férec C. 2009. Chronic pancreatitis: genetics and pathogenesis. Annu Rev Genomics Hum Genet 10: 63–87. PubMed ID: 19453252
  • Ellis, I, Lerch, MM, Whitcomb, DC. 2001. Genetic testing for hereditary pancreatitis: guidelines for indications, counselling, consent and privacy issues. Pancreatology 1:405-415. PubMed ID: 12120217
  • Human Gene Mutation Database (Bio-base).
  • Joergensen, MT, Brusgaard, K, Crüger, DG, Gerdes, AM, Schaffalitzky de Muckadell, OB. 2010. Genetic, epidemiological, and clinical aspects of hereditary pancreatitis: a population-based cohort study in Denmark. Am. J. Gastroenterol. 105:1876-1883. PubMed ID: 20502448
  • Keiles S, Kammesheidt A. 2006. Identification of CFTR, PRSS1, and SPINK1 mutations in 381 patients with pancreatitis. Pancreas 33: 221–227. PubMed ID: 17003641
  • Le Maréchal C, Masson E, Chen J-M, Morel F, Ruszniewski P, Levy P, Férec C. 2006. Hereditary pancreatitis caused by triplication of the trypsinogen locus. Nature Genetics 38: 1372–1374. PubMed ID: 17072318
  • Rebours V, Lévy P, Ruszniewski P. 2012. An overview of hereditary pancreatitis. Dig Liver Dis 44: 8–15. PubMed ID: 21907651
  • Yadav D, Whitcomb DC. 2010. The role of alcohol and smoking in pancreatitis. Nat Rev Gastroenterol Hepatol 7: 131–145. PubMed ID: 20125091

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page


Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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ORDER OPTIONS

View Ordering Instructions

1) Select Test Method (Backbone)


1) Select Test Type


2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
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