CEL, CFTR, SBDS, UBR1
The Pancreatic Insufficiency Panel is designed to establish the genetic causes of pancreatic insufficiency or determine an individual’s risk of developing this condition.
Pancreatic insufficiency is the inability of the pancreas to produce sufficient pancreatic digestive enzymes. It is commonly associated with pancreatitis and associated conditions. Chronic pancreatitis presents with mild-severe abdominal pain and exocrine pancreatic insufficiency, leading to digestive issues and endocrine pancreatic insufficiency. These conditions can lead to glucose intolerance / type I diabetes mellitus. Pancreatitis can occur as a part of a syndrome (for example, Johanson Blizzard syndrome or Shwachman-Diamond syndrome (SBDS)) or as an isolated finding. It can be caused by underlying genetic factors or non-genetic environmental factors (e.g., alcohol abuse, infection or trauma) or a combination of both. Pancreatitis is usually categorized as hereditary, familial or idiopathic. Depending on the underlying genetic etiology, it can be inherited in autosomal dominant, autosomal recessive or in a polygenic manner.
- Pancreatic Insufficiency of unknown etiology with overlapping clinical symptoms
- Maturity-onset diabetes of the young, type VIII
- Shwachman-Diamond syndrome
- Johanson Blizzard syndrome
- Presymptomatic diagnosis for at-risk individuals with a family history of pancreatitis of unknown genetic basis
This test is performed by enrichment of the coding exons, flanking intronic and untranslated regions (5’ and 3’), as well as known pathogenic variants (HGMD 2018.1) in the promoter and deep intronic regions of the genes specified above using oligonucleotide probe hybridization followed by next-generation sequencing with >50X coverage at every target base. All pathogenic and novel variants, as well as variants of unknown (indeterminate) significance, as determined bioinformatically, are confirmed by Sanger sequencing. Regions with <50X will be filled in by Sanger sequencing. A detailed non-coding variant list is available upon request.
One study identified that 48.2 percent of patients with idiopathic pancreatitis have evidence of a genetic basis for their pancreatitis (Masson et al. 2013). Isolated pathogenic variants in CFTR, CTRC, and SPINK1 have been found to be associated with increased susceptibility to pancreatitis. Pancreatitis and subsequent pancreatic insufficiency are cardinal features in syndromes such as Johanson-Blizzard syndrome, Shwachman-Diamond syndrome and CEL maturity-onset diabetes of the young.
How to Order
Download Heritable Pancreatic Disease requisition. Single gene sequencing and targeted variant analysis are also available for all genes in the Pancreatic Insufficiency Panel.
Koziel, D., S. Gluszek, et al. (2015) "Genetic Mutations in SPINK1, CFTR, CTRC Genes in Acute Pancreatitis." BMC Gastroenterology 15: 70.
LaRusch, J. and D. Whitcomb. (2011) "Genetics of pancreatitis." Curr Opin Gastroenterol 27(5): 467–474.
Ravi Kanth, V. and R. Nageshwar. (2014) "Genetics of acute and chronic pancreatitis: An update." World J Gastrointest Pathophysio 5(4): 427-37.
Whitcomb, D. (2013) "Genetic Risk Factors for Pancreatic Disorders." Gastroenterology 144(6): 1292–1302.