Polymerase Chain Reaction/Sequencing
Polymerase Chain Reaction/Sequencing
For adults with idiopathic pancreatitis if other components of panel (CFTR, PRSS1, SPINK1) have been sequenced without providing a complete explanation for the pancreatitis
Polymerase Chain Reaction/Sequencing and Multiplex Ligation Dependent Probe Amplification
Preferred test for individuals with idiopathic pancreatitis who:
- Are <20 years of age OR
- Have two affected first-degree relatives
Polymerase Chain Reaction/Sequencing
For adults with idiopathic pancreatitis if other components of panel (CFTR, CTRC, PRSS1) have been sequenced without providing a complete explanation for the pancreatitis
Polymerase Chain Reaction/Sequencing
May be used to test for variants causative for mild cystic fibrosis in individuals with idiopathic pancreatitis
Related Tests
Polymerase Chain Reaction/Sequencing
Useful when a pathogenic familial variant identifiable by sequencing is known
Multiplex Ligation-dependent Probe Amplification
Use to asses for large deletion/duplication in CFTR, PRSS1, or SPINK1 previously identified in a family member
Pancreatitis is a relatively common disorder with multiple etiologies that causes inflammation in the pancreas. Acute pancreatitis (AP) is a result of sudden inflammation, and patients may present with increased pancreatic enzyme concentrations. Chronic pancreatitis (CP) is a syndrome of progressive inflammation that may lead to permanent damage to pancreatic structure and function. Genetic testing can be utilized to determine a genetic cause of idiopathic or hereditary AP or CP and/or to assess risk of disease in family members.
Disease Overview
Incidence/Prevalence
Genetics
Genes
- CFTR, CTRC, PRSS1, SPINK1
- Other genes have been reported to be associated with CP but are not currently included in the ARUP test menu
Inheritance
- PRSS1 is autosomal dominant with gain-of-function variants
- CFTR, CTRC, SPINK1 are autosomal recessive/digenic
Test Interpretation
Sensitivity/Specificity in Idiopathic Pancreatitis
- Clinical sensitivity for contributory or causative variants
- Analytical sensitivity/specificity: 99%
Results
Result | Interpretation |
---|---|
Positive |
One of the following:
|
Negative | No pathogenic variants detected in any of the genes; reduces the risk for hereditary pancreatitis but genetic etiology is not excluded |
Uncertain | Variant(s) of uncertain clinical significance detected; may be disease-causing or benign |
Limitations
- Regulatory region variants, deep intronic variants, and some large deletions/duplications will not be detected.
- Diagnostic errors can occur due to rare sequence variations.
- Variants in currently unknown genes may be associated with pancreatitis.
References
-
25333398
Conwell DL, Lee LS, Yadav D, et al. American Pancreatic Association practice guidelines in chronic pancreatitis: evidence-based report on diagnostic guidelines. Pancreas. 2014;43(8):1143-1162.
PubMed -
29880587
Gupte A, Goede D, Tuite R, et al. Chronic pancreatitis. BMJ. 2018;361:k2126.
PubMed -
GeneReviews - PRSS1-related hereditary pancreatitis
Shelton C, Solomon S, LaRusch J, et al. PRSS1-related hereditary pancreatitis. In: Adam MP, Ardinger HH, Pagon RA, et al, editors. GeneReviews, University of Washington; 1993-2020. [Last Update: Apr 2019; Accessed: Feb 2020]
Online -
9219780
Sossenheimer MJ, Aston CE, Preston RA, et al. Clinical characteristics of hereditary pancreatitis in a large family, based on high-risk haplotype. The Midwest Multicenter Pancreatic Study Group (MMPSG). Am J Gastroenterol. 1997;92(7):1113-1116.
PubMed -
23951356
Masson E, Chen JM, Audrézet MP, 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;8(8):e73522.
PubMed
21844754
LaRusch J, Whitcomb DC. Genetics of pancreatitis. Curr Opin Gastroenterol. 2011;27(5):467-474.
23622135
Yadav D, Lowenfels AB. The epidemiology of pancreatitis and pancreatic cancer. Gastroenterology. 2013;144(6):1252-1261.
Preferred test for individuals with history of idiopathic pancreatitis