Chronic Hereditary Pancreatitis via the SPINK1 Gene
Summary and Pricing 
Test Method
Exome Sequencing with CNV Detection
| Test Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
|---|---|---|---|---|---|
| 8957 | SPINK1 | 81404 | 81404,81479 | $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 platform).
Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing platform).
The Sanger Sequencing method for this test is NY State approved.
For Sanger Sequencing click here.Turnaround Time
3 weeks on average for standard orders or 2 weeks 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.
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 and 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 chronic pancreatitis (Joergensen et al. 2010). Genetic testing can aid in differential diagnosis of chronic pancreatitis from other disorders such as Shwachman-Diamond syndrome and Johanson-Blizzard syndrome which also present with pancreatitis (LaRusch et al. 2014).
Genetics
Hereditary chronic pancreatitis (HP) occurs at an estimated incidence of 0.3/100,000 in western countries (Joergensen et al. 2010) and presents as autosomal dominant or recessive with incomplete penetrance (80%) depending upon the gene that is involved. Mutations in the serine protease inhibitor Kazal type 1 (SPINK1) gene are known to be causative for autosomal recessive HP (Keiles et al. 2006). Compound heterozygosity for mutations in SPINK1 and either CTRC/CFTR or CASR suggests a digenic mode of inheritance (Masson et al. 2013; Chen and Ferec 2009). In rare cases, SPINK1 mutations have been found in chronic pancreatitis patients with a PRSS1 mutation.
The SPINK1 gene encodes a pancreatic secretory trypsin inhibitor which protects the pancreas from damage due to recurrent or persistent trypsin activation (Horii et al. 1987). SPINK1 causative mutations have also been identified in individuals with tropical calcific pancreatitis (OMIM#608189) (Chandak et al. 2002). Mutations in PRSS1, CFTR, and CTRC are also known to be involved in the onset of HP (OMIM#167800) (Audrezet et al. 2002). The types of mutations reported in SPINK1 include missense, splicing, regulatory, deletions and insertions (Human Gene Mutation Database). The c.101A>G (p.Asn34Ser) and c.194+2T>C variants are commonly found causative mutations within the US/Europe and Asian populations (LaRusch et al. 2014).
Clinical Sensitivity - Sequencing with CNV PGxome
The p.N34S mutation in exon 4 of SPINK1 is the most common alteration identified in individuals with SPINK1-associated HP (http://www.uni-leipzig.de/pancreasmutation/db.html). Our full gene sequencing test is expected to detect >98% of SPINK1 causative mutations.
Testing Strategy
This test provides full coverage of all coding exons of the SPINK1 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).
This test also provides coverage ~240 bp upstream from the start codon.
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 be considered for genetic testing (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. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in SPINK1.
Individuals with the following criteria should be considered for genetic testing (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. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in SPINK1.
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| SPINK1 | 167790 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Diseases
| Name | Inheritance | OMIM ID |
|---|---|---|
| Pancreatitis, Chronic | AD | 167800 |
| Tropical Calcific Pancreatitis | AR, AD | 608189 |
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
- Chandak GR, Idris MM, Reddy DN, Bhaskar S, Sriram PVJ, Singh L. 2002. Mutations in the pancreatic secretory trypsin inhibitor gene (PSTI/SPINK1) rather than the cationic trypsinogen gene (PRSS1) are significantly associated with tropical calcific pancreatitis. Journal of medical genetics 39: 347–351. PubMed ID: 12011155
- 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
- Horii A, Kobayashi T, Tomita N, Yamamoto T, Fukushige S, Murotsu T, Ogawa M, Mori T, Matsubara K. 1987. Primary structure of human pancreatic secretory trypsin inhibitor (PSTI) gene. Biochem. Biophys. Res. Commun. 149: 635–641. PubMed ID: 3501289
- 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
- LaRusch J, Solomon S, Whitcomb DC. 2014. Pancreatitis Overview. In: Pagon RA, Adam MP, Ardinger HH, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews(®), Seattle (WA): University of Washington, Seattle. PubMed ID: 24624459
- Masson, E, Chen, JM, Audrézet, MP, Cooper, DN, Férec, C. 2013. 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 8:e73522. PubMed ID: 23951356
- 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
If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.
Specimen Types
Specimen Requirements and Shipping Details
PGxome (Exome) Sequencing Panel
PGnome (Genome) Sequencing Panel
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