Relation between Mutations of the Cystic Fibrosis Gene and Idiopathic Pancreatitis

Abstract

In a group of patients referred for evaluation of idiopathic pancreatitis, there was a strong association between mutations in the CFTR gene and pancreatitis. The abnormal CFTR genotypes in these patients with pancreatitis resemble those associated with male infertility.

Best practice guidelines for molecular genetic diagnosis of cystic fibrosis and CFTR-related disorders – updated European recommendations

“…More than 1500 sequence variations have been reported in the CFTR gene, often with geographic or ethnic variations in frequency 6 -8 and which are found in both CF and related phenotypes, named CFTR-related disorders (CFTR-RD). These are clinical entities associated with CFTR dysfunction but where the diagnosis of CF cannot be unambiguously established; 1 for example, congenital bilateral absence of vas deferens (CBAVD) 9 -13 disseminated bronchiectasis, 14,15 chronic pancreatitis, 16,17 or chronic rhinosinusitis. 18,19 CFTR gene analyses are performed in specialist clinical molecular genetics laboratories closely associated with clinical genetic services or research facilities, and also in private laboratories; lists of European laboratories offering CFTR genetic testing are available at www.orpha.net or at www.eurogentest.org/web/qa/basic.xhtml.…”

Mutation analysis of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, the cationic trypsinogen (PRSS1) gene, and the serine protease inhibitor, Kazal type 1 (SPINK1) gene in patients with alcoholic chronic pancreatitis

“…Some evidence exists that at least in a small proportion of patients with ICP, a mutation of one or both alleles of either the cystic fibrosis transmembrane conductance regulator (CFTR; OMIM: 602421) gene 6,7 or the serine protease inhibitor, Kazal type 1 (SPINK1; OMIM: 167790) gene 8,9 can be identified. Severe mutations in both alleles of the CFTR results in the commonly recognized cystic fibrosis (CF) clinical features of abnormal sweat chloride concentrations, pancreatic insufficiency, and progressive pulmonary disease.…”

Acute Pancreatitis is a Chronic Disease

“…The basic pathogenetic mechanism is considered to be the cumulative effect of successive acute insults, or the so-called necrosis-fibrosis sequence, on a background of oxidative stress [8]. In the Western world, the principal causative factor is alcohol [5], although various other effect modifiers such as smoking [9,10], diet [11,12] and genetic predisposition [13][14][15] are thought to play a part in its multifactorial aetiology. Clinical manifestations of chronic pancreatitis, which are variable in extent and time-course, are pain, malabsorption and diabetes.…”