SCIENTIFIC BACKGROUND

CASR, CFTR, CPA1, CTRC, PRSS1, SPINK1

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Scientific Background

Pancreatitis is generally divided into acute and chronic forms. Chronic pancreatitis describes a complex, highly variable and continuous inflammatory syndrome, defined by initially repetitive episodes of acute pancreatitis, which may develop into chronic pancreatitis in the long term. Progressive fibrosis of the pancreatic parenchyma, parenchymal calcifications and pancreatic duct calculi ultimately lead to irreversible destruction of the organ due to the failure of exocrine and endocrine functions. The risk of developing ductal adenocarcinoma of the pancreas is greatly increased.

 

Clinical signs include repeated attacks of abdominal pain with elevated serum levels of pancreatic enzymes, typical pancreatic pain, steatorrhea and diabetes mellitus. The incidence of chronic pancreatitis in industrialized countries is estimated at 3.5 to 10:100,000, with chronic alcohol abuse being the main cause. Other risk factors include genetic changes, hypertriglyceridemia, autoimmunity and hypercalcemia. In an attempt to classify the disease into different clinical entities, terms such as hereditary, idiopathic, familial and sporadic pancreatitis are used in the literature. There is no standard, generally valid definition of pancreatitis; in particular, the term ‘hereditary pancreatitis’ is used in various contexts.

 

According to current knowledge, changes in the genes PRSS1 (cationic trypsinogen), SPINK1 (serine protease inhibitor Kazal type I), CFTR (cystic fibrosis transmembrane conductance regulator) and CTRC (chymotrypsin C) are involved to varying degrees in the development and penetrance of chronic pancreatitis, either as a cause or predisposing factor. According to recent studies, variants in the CPA1 and CASR genes could also be found in these patients. Diverse inheritance, including digenic inheritance (transheterozygosity), is observed, i.e., pathogenic variants in two of the above-mentioned genes are present together. Pathogenic variants in the above-mentioned genes can be detected in about 49% of patients with chronic pancreatitis.

 

References

Mayerle et al. 2019, Gastroenterology 156(7):1951 / Hasan et al. 2018, Gastrointest Endosc Clin N Am 28(4):587 / Witt 2010, Dig Dis 28:702-708 / Chen et al. 2009, Annu Rev Genomics Hum Genet 10:3.1 / Keim 2008, World J Gastroenterol 14:1011 / Teich et al. 2006, Hum Mutat 27:721 / Audrezet et al. 2002, Eur J Hum Genet 10:100 / Le Marechal et al. 2001, BMC Genetics 2:19 / Witt et al. 2000, Nat Genet 25:213

GENES

CASR, CFTR, CPA1, CTRC, PRSS1, SPINK1

ASSOCIATED TESTS

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