Screening for human cationic trypsinogen (PRSS1) and trypsinogen inhibitor gene (SPINK1) mutations in a Finnish family with hereditary pancreatitis

Räty, Sari; Piironen, Anneli; Babu, M. Hari; Pelli, Hanna; Sand, Juhani; Uotila, Sanna T.H.; Nordback, Isto; Herzig, Karl‐Heinz

doi:10.1080/00365520701206738

Cited by 7 publications

(7 citation statements)

References 29 publications

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“…The frequency of this pancreatitis reason is described in the literature at the level of 2.5–9.8% [ 9 , 17 ] In 2012, the Sultan showed a high prevalence of genetic mutations (in the SPINK, PRSS1, and CFTR genes) in patients with recurrent and chronic pancreatitis without other causes of these diseases (anatomic and metabolic) [ 18 ]. It is known that mutations in the gene PRSS1 (two types: R122H and N29I) are responsible for hereditary pancreatitis, and SPINK1 gene mutation is strongly associated (about 20% of patients) with idiopathic chronic pancreatitis in children and adolescents [ 19 ]. In recent years, some other mutations associated with the early occurrence of acute and chronic pancreatitis have been described – mutations in the CPA1 gene encoding carboxypeptidase A1 (one of the pancreatic metalloproteinases) [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

Acute pancreatitis in children

Grzybowska-Chłebowczyk

Jasielska²,

Flak-Wancerz³

et al. 2018

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IntroductionThe acute pancreatitis is a rare disease, but it has started to be diagnosed more often in children.AimThe aim of the study was single-centre, retrospective analysis of the incidence, aetiology, and clinical course of acute pancreatitis in children.Material and methodsWe analysed the medical records of patients with acute pancreatitis hospitalised in the Gastroenterology Unit of the Paediatrics Department, Medical University of Silesia from Jan 2004 to Dec 2013.ResultsThere were 76 cases of acute pancreatitis among 51 children (average age: 12.07 years) hospitalised in the Gastroenterology Unit between January 2004 and December 2013. The diagnosis of acute pancreatitis was performed on the basis of INSPIRE criteria and modified Atlanta classification. Patients were divided into groups: I – 1–12 years old, which included 20 (39.21%) children and II – 13–18 years old, with 31 (60.78%) children. The idiopathic aetiology was the most common cause of acute pancreatitis, occurring in 22 (43.1%) children, and in 15 cases the aetiology of the disease was biliary (29.4%). Genetically determined causes were diagnosed in 8 (15.7%) patients, the PRSS1 mutation in four patients, mutation in SPINK1 in 1 child, and CFTR gene mutation in 1 child. Two children simultaneously had two genes mutations (CFTR, SPINK1), and during the considered period had more than one episode of acute pancreatitis.ConclusionsAcute pancreatitis of idiopathic aetiology was most common among the examined children, and this should encourage the continued search for the causes of disease, especially genetic, and with particular emphasis on younger age group.

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Section: Discussionmentioning

confidence: 99%

Acute pancreatitis in children

Grzybowska-Chłebowczyk

Jasielska²,

Flak-Wancerz³

et al. 2018

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“…The most frequent SPINK1 mutation is p.N34S. Several other mutations, including p.M1, p.L14P, p.L14R, c.[1-215G>A;194+2T>C] and p.R67C, are possibly associated with chronic pancreatitis [3,14,23,24,25,26]. More recent contributions have confirmed the strong association between SPINK1 and CFTR [27,28].…”

Section: Introductionmentioning

confidence: 86%

“…In 1996, Whitcomb et al [7] identified the first mutation associated with hereditary pancreatitis, namely the R122H mutation in the cationic trypsinogen gene (PRSS1). Several other mutations (A16V, K23R, N29I, N29T, R122C) and triplication as well as duplication of the PRSS1 locus have been subsequently described [4,12,13,14,15,16,17,18]. …”

Section: Introductionmentioning

confidence: 99%

Clinical and Morphological Characteristics of Sporadic Genetically Determined Pancreatitis as Compared to Idiopathic Pancreatitis: Higher Risk of Pancreatic Cancer in CFTR Variants

Hamoir¹,

Pepermans

Piessevaux³

et al. 2013

Digestion

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Background/Aims: Idiopathic pancreatitis is considered to be a multigenic and multifactorial disease. Genetically determined pancreatitis is associated with mutations in the PRSS1,SPINK1 and CFTR genes. This study aimed at examining the clinical and morphological characteristics of patients diagnosed with genetically determined sporadic pancreatitis. Methods: Inclusion criteria were the presence of PRSS1,CFTR or SPINK1 gene mutations in patients with idiopathic recurrent or chronic pancreatitis. Patients with hereditary pancreatitis were excluded. Age- and sex-matched patients with idiopathic pancreatitis and negative genetic testing served as controls (n = 68). Results: Genetic testing was performed in 351 probands referred to our centre since 1999. Sixty-one patients (17.4%) carried at least 1 detected mutation in 1 of the 3 tested genes (34 CFTR, 10 PRSS1 and 13 SPINK1 mutations), and 4 patients showed a combination of mutations. Follow-up has been currently extended to a median of 5 years (range 1-40). Similar clinical features were noted in the case and matched groups except for an earlier age of onset of pancreatic symptoms and a higher incidence of pancreatic cancer in the case group and in patients with CFTR mutations compared to the control group (p < 0.05). The standardized incidence ratio, the ratio of observed to expected pancreatic cancers, averaged 26.5 (95% confidence interval 8.6-61.9). All pancreatic cancer patients were smokers. Conclusion: Clinical parameters of patients with sporadic idiopathic pancreatitis and gene mutations are similar to those of age- and sex-matched patients without gene mutations, except for the age of pancreatic disease onset. A significantly higher occurrence of pancreas cancer was observed in the case group, particularly in those patients carrying CFTR mutations. We therefore suggest to include patients with CFTR variants presenting with risk factors in a screening and surveillance programme and to strongly advise them to stop smoking.

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“…(8,9) About 100 families have been documented worldwide. (4) which has been screened in different countries (3,(10)(11)(12)(13)(14)(15)(16) HP is a progressive inflammatory disease in which pancreatic secretory parenchyma is destroyed and replaced by fibrous tissue (17), eventually leading to malnutrition and diabetes. (18) several studies shows that, Patients with HP have a markedly increased risk of pancreatic cancer compared with the general population up to 40-50% .…”

Section: Introductionmentioning

confidence: 99%

Novel mutations within PRSS1 Gene that could potentially cause hereditary pancreatitis: Using Comprehensive in silico Approach

Mustafa

et al. 2019

Preprint

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Background: Hereditary pancreatitis (HP) is an autosomal dominant disorder with incomplete penetrance characterized by recurring episodes of severe abdominal pain often presenting in childhood. The comprehensive in silico analysis of coding SNPs, and their functional impacts on protein level, still remains unknown. In this study, we aimed to identify the pathogenic SNPs in PRSS1 gene by computational analysis approach. Materials and Methods: We carried out in silico analysis of structural effect of each SNP using different bioinformatics tools to predict Single-nucleotide polymorphisms influence on protein structure and function. Result: Two novel mutations out of 339 nsSNPs that are found be deleterious effect on the PRSS1 structure and function. Conclusion: This is the first in silico analysis in PRSS1 gene, which will be a valuable resource for future targeted mechanistic and population-based studies.

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Screening for human cationic trypsinogen (PRSS1) and trypsinogen inhibitor gene (SPINK1) mutations in a Finnish family with hereditary pancreatitis

Abstract: In the investigated Finnish pedigree with HP, the PRSS1 mutation R122H is linked with chronic disease. Although the SPINK1 mutation (N34S) was also observed in two individuals, it was not linked with the disease.

Cited by 7 publications

References 29 publications

Acute pancreatitis in children

Acute pancreatitis in children

Clinical and Morphological Characteristics of Sporadic Genetically Determined Pancreatitis as Compared to Idiopathic Pancreatitis: Higher Risk of Pancreatic Cancer in CFTR Variants

Novel mutations within PRSS1 Gene that could potentially cause hereditary pancreatitis: Using Comprehensive in silico Approach

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