Mutational screening of the cationic trypsinogen gene in a large cohort of subjects with idiopathic chronic pancreatitis

Chen, Jian‐Min; Bis, AP; Bodic, L. Le; Ruszniewski, Philippe; Robaszkiewicz, Michel; Deprez, Pierre Henri; Raguénès, Odile; Quéré, I.; Andriulli, Angelo; Férec, Claude

doi:10.1034/j.1399-0004.2001.590308.x

Cited by 65 publications

(32 citation statements)

References 35 publications

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“…In this study, the simple PRSS1 and PSTI genes ± the former is composed of only five exons encoding 247 amino acids 25 and the latter consists of only four exons encoding 79 amino acids 26 ± were subjected to our previously established DGGE analyses, which have been demonstrated to be both sensitive and efficient, as well as capable of detecting known mutations and identifying novel variants. 6,10,21 In contrast, it is not easy to perform a complete analysis of the CFTR gene, which consists of 27 exons encoding 1480 amino acids. 27 Indeed, to date, most of the relevant studies have investigated only a selected subset of the most common CFTR mutations in CP.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2002

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In the last 5 years, mutations in three genes, the cystic fibrosis transmembrane conductance regulator (CFTR) gene, the cationic trypsinogen (PRSS1) gene, and the pancreatic secretory trypsin inhibitor (PSTI) gene, have been found to be associated with chronic pancreatitis (CP). In this study, using established mutation screening methods, we systematically analysed the entire coding sequences and all exon/intron junctions of the three genes in 39 patients with idiopathic CP (ICP), with a view to evaluating the relative contribution of each gene to the aetiology of the disease. Our results demonstrate that, firstly,`gain-of-function' mutations in the PRSS1 gene may occasionally be found in an obvious ICP subject. Secondly, presumably`loss-of-function' mutations in the PSTI gene appear to be frequent, with a detection rate of at least 10% in ICP and, finally, abnormal CFTR alleles are common: at least 20% of patients carried one of the most common CFTR mutations, and about 10% of patients were compound heterozygotes, having at least one`mild' allele. Thus, in total, about 30% of ICP patients carried at least one abnormal allele in one of the three genes, and this is the most conservative estimate. Moreover, a trans-heterozygous state with sequence variations in the PSTI/ CFTR genes was found in three patients. However, an association between the 5T allele in intron 8 of the CFTR gene and ICP remains unproven.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2002

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“…The entire PRSS1 gene was sequenced in these patients. Only three patients had mutations, one with R122H and two patients with A16V [27] . A genetic background has also been investigated in patients with idiopathic juvenile chronic pancreatitis, a disease which closely mimics the clinical pattern of hereditary pancreatitis [28] .…”

Section: Cationic Trypsinogen Gene Mutations In Non-hereditary Pancrementioning

confidence: 98%

Hereditary pancreatitis

Charnley¹

2003

WJG

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Hereditary pancreatitis is an autosomal dominant condition, which results in recurrent attacks of acute pancreatitis, progressing to chronic pancreatitis often at a young age. The majority of patients with hereditary pancreatitis express one of two mutations (R122H or N29I) in the cationic trypsinogen gene (PRSS1 gene). It has been hypothesised that one of these mutations, the R122H mutation causes pancreatitis by altering a trypsin recognition site so preventing deactivation of trypsin within the pancreas and prolonging its action, resulting in autodigestion. Families with these two mutations have been identified in many countries and there are also other rarer mutations, which have also been linked to hereditary pancreatitis.Patients with hereditary pancreatitis present in the same way as those with sporadic pancreatitis but at an earlier age. It is common for patients to remain undiagnosed for many years, particularly if they present with non-specific symptoms. Hereditary pancreatitis should always be considered in patients who present with recurrent pancreatitis with a family history of pancreatic disease. If patients with the 2 common mutations are compared, those with the R122H mutation are more likely to present at a younger age and are more likely to require surgical intervention than those with N29I. Hereditary pancreatitis carries a 40 % lifetime risk of pancreatic cancer with those patients aged between 50 to 70 being most at risk in whom screening tests may become important.

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“…The most frequently observed SPINK1 mutations are N34S and P55S, occurring mainly in Europe and the USA. Many studies provide evidence for the relationship between N34S mutation and chronic pancreatitis of varied aetiology, with a frequency of approximately 9.7% [15,56,[69][70][71]. The mechanism combining SPINK1 p.N34S mutation with pancreatitis remains unexplained [71].…”

Section: Spink1mentioning

confidence: 99%

“…An asparagineisoleucine replacement at position 29 of cationic trypsinogen results in an increase in resistance to autolytic processes [55]. The A16V mutation is the third most frequent PRSS1 mutation with changeable penetration, most often in the group of patients with idiopathic pancreatitis [47,56]. The results of studies conducted by Nemoda [51] in 2006 confirmed that the A16V mutant protein, contrary to R122H and N29I, does not itself increase auto-activation of cationic trypsinogen; however, the stimulation of autoactivation by chymotrypsin C plays a role in chronic pancreatitis related with A16V mutation [51].…”

Section: Prss1mentioning

confidence: 99%