For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
519
views
31
references
 Top references
cited by
11
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      451
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Comprehensive screening for PRSS1, SPINK1, CFTR, CTRC and CLDN2 gene mutations in Chinese paediatric patients with idiopathic chronic pancreatitis: a cohort study

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Objective

          Genetic alterations may contribute to chronic pancreatitis (CP) in Chinese young patients. This study was designed to investigate mutations of cationic trypsinogen ( PRSS1), pancreatic secretory trypsin inhibitor or serine protease inhibitor Kazal type 1 ( SPINK1), cystic fibrosis transmembrane conductance regulator (CFTR), chymotrypsin C (CTRC) and CLDN2 genes and the copy number variations (CNVs) of PRSS1 and asses associations with the development of idiopathic CP (ICP) in Chinese children.

          Design

          Retrospective.

          Setting

          A single center.

          Participants

          75 ICP Chinese children (40 boys and 35 girls).

          Primary and secondary outcome measures

          Mutations of PRSS1, SPINK1, CFTR, CTRC and CLDN2 genes and CNVs.

          Results

          7 patients had heterozygous mutations in PRSS1, that is, N29I (n=1), R122H or R122C (n=6). The CNVs of PRSS1 in five patients had abnormal copies (1 copy (n=4), five copies (n=1)). 43 patients had IVS3+2T>C (rs148954387) (10 homozygous and 33 heterozygous) in SPINK1. None of the PRSS1 mutation patients carried a SPINK1 mutation. Frequency of PRSS1 and SPINK1 mutations was 9.3% and 57.3%, respectively, with an overall frequency of 66.6% (50/75). In addition, one patient had a novel deletion of CFTR (GCTTCCTA from c.500 to c.508 leading to the shortened polypeptide molecule via a stop codon). Another patient had a novel missense in CLDN2 exon 2 (c.592A>C mutation). Clinically, patients with SPINK1 mutations had a higher rate of pancreatic duct stones, pancreatic pseudocyst and pancreatic calcification than those without SPINK1 mutations (p<0.05).

          Conclusions

          SPINK1 mutations were more commonly associated with Chinese children with ICP. SPINK1 IVS3+2T>C mutation may play an important role in the pathogenesis of Chinese paediatric ICP. However, further study is needed to confirm and to investigate the role of these genes in the development of Chinese ICP.

          Related collections

          Most cited references31

          • Record: found
          • Abstract: found
          • Article: not found

          Clinical and genetic characteristics of hereditary pancreatitis in Europe.

          Richard M. Charnley, Jan O Jansen, Giorgio Cavallini … (2004)
          Hereditary pancreatitis is an autosomal dominant disease that is mostly caused by cationic trypsinogen (PRSS1) gene mutations. The aim was to determine phenotype-genotype correlations of families in Europe. Analysis of data obtained by the European Registry of Hereditary Pancreatitis and Pancreatic Cancer was undertaken using multilevel proportional hazards modelling. There were 112 families in 14 countries (418 affected individuals): 58 (52%) families carried the R122H, 24 (21%) the N29I, and 5 (4%) the A16V mutation, 2 had rare mutations, and 21 (19%) had no PRSS1 mutation. The median (95% confidence interval [CI]) time to first symptoms for R122H was 10 (8, 12) years of age, 14 (11, 18) years for N29I, and 14.5 (10, 21) years for mutation negative patients (P = 0.032). The cumulative risk (95% CI) at 50 years of age for exocrine failure was 37.2% (28.5%, 45.8%), 47.6% (37.1%, 58.1%) for endocrine failure, and 17.5% (12.2%, 22.7%) for pancreatic resection for pain. Time to resection was significantly reduced for females (P < 0.001) and those with the N29I mutation (P = 0.014). The cumulative risk (95% CI) of pancreatic cancer was 44.0% (8.0%, 80.0%) at 70 years from symptom onset with a standardized incidence ratio of 67% (50%, 82%). Symptoms in hereditary pancreatitis start in younger patients and endpoints take longer to be reached compared with other forms of chronic pancreatitis but the cumulative levels of exocrine and endocrine failure are much higher. There is an increasingly high risk of pancreatic cancer after the age of 50 years unrelated to the genotype.
          Article 0 comments Cited 113 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            SPINK1/PSTI polymorphisms act as disease modifiers in familial and idiopathic chronic pancreatitis.

            Ann Finch, D Whitcomb, J. Neoptolemos … (2000)
            Gain-of-function trypsin mutations cause acute pancreatitis and chronic pancreatitis. Loss of trypsin inhibitor function may have similar effects. We investigated the prevalence of SPINK1 (PSTI) mutations in familial pancreatitis, idiopathic chronic pancreatitis, and controls. Genetic-linkage studies were performed in 5 familial pancreatitis families. The entire SPINK1 gene was sequenced in 112 affected individuals and 95 control DNA samples, and exon 3 was sequenced in 95 additional controls. X-ray crystallography-based model building and statistical studies were performed. Significant linkage between pancreatitis and 5q31.1-2 was excluded. Novel SPINK1 mutations, one D50E mutation, one IVS3+125 C>A, and five IVS3+184 T>A intronic polymorphisms were identified. The N34S and P55S mutations were observed in 29 of 112 patients (25%) as N34S/N34S (n = 7), N34S/wt (n = 19), N34S/P55S (n = 2), and N34S/D50E (n = 1). Three hundred eighty control alleles revealed 3 N34S (0.77%), 2 P55S (0.53%), and no D50E mutations. Age of disease onset and severity were similar between homozygous and heterozygous patients. Structural modeling revealed several possible pathophysiologic mechanisms for the N34S mutation. SPINK1 mutations are common in the population (approximately 2%), but are clearly associated with pancreatitis. The mutation-associated risk is low. Modeling and familial clustering suggest that SPINK1 mutations are disease modifying, possibly by lowering the threshold for pancreatitis from other genetic or environmental factors, but by themselves do not cause disease.
            Article 0 comments Cited 77 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              The natural history of hereditary pancreatitis: a national series.

              C Maréchal, F Maire, P. Hammel … (2008)
              The prevalence and natural history of hereditary pancreatitis (HP) remain poorly documented. The aims of this study were to assess genetic, epidemiological, clinical and morphological characteristics of HP in an extensive national survey. A cohort comprising all HP patients was constituted by contacting all gastroenterologists and paediatricians (response rate 84%) and genetics laboratories (response rate 100%) in France (60,200,000 inhabitants). Inclusion criteria were the presence of mutation in the cationic trypsingen gene (PRSS1 gene), or chronic pancreatitis in at least two first-degree relatives, or three second-degree relatives, in the absence of precipitating factors for pancreatitis. 78 families and 200 patients were included (181 alive, 6673 person-years, males 53%, alcoholism 5%, smoking 34%). The prevalence was 0.3/100,000 inhabitants. PRSS1 mutations were detected in 68% (R122H 78%, N29I 12%, others 10%). Penetrance was 93%. Median age at first symptom, diagnosis and date of last news, were 10 (range 1-73), 19 (1-80) and 30 (1-84) years, respectively. HP was responsible for pancreatic pain (83%), acute pancreatitis (69%), pseudocysts (23%), cholestasis (3%), pancreatic calcifications (61%), exocrine pancreatic insufficiency (34%, median age of occurrence 29 years), diabetes mellitus (26%, median age of occurrence 38 years) and pancreatic adenocarcinoma (5%, median age 55 years). No differences in clinical and morphological data according to genetic status were observed. 19 patients died, including 10 directly from HP (8 from pancreatic adenocarcinoma). The prevalence of HP in France is at least 0.3/100,000. PRSS1 gene mutations are found in 2/3 with a 93% penetrance. Mutation type is not correlated with clinical/morphological expression. Pancreatic adenocarcinoma is the cause of nearly half the deaths.
              Article 0 comments Cited 64 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-ta): BMJ Open
                Journal ID (iso-abbrev): BMJ Open
                Journal ID (hwp): bmjopen
                Journal ID (publisher-id): bmjopen
                Title: BMJ Open
                Publisher: BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                ISSN (Electronic): 2044-6055
                Publication date Collection: 2013
                Publication date (Electronic): 2 September 2013
                Volume: 3
                Issue: 9
                Electronic Location Identifier: e003150
                Affiliations
                [1 ]Department of Gastroenterology, Changhai Hospital, The Second Military Medicine University , Shanghai, China
                [2 ]Key Laboratory of Developmental Genetics and Neuropsychiatric Diseases (Ministry of Education), Bio-X Institutes, Shanghai Jiao Tong University , Shanghai, China
                Author notes
                [Correspondence to ] Professor Zhao-Shen Li; zhaoshenli@ 123456hotmail.com or Zhuan Liao; liao.zhuan@ 123456gmail.com

                WW, X-TS, X-LW and D-ZZ contributed equally.

                Article
                Publisher ID: bmjopen-2013-003150
                DOI: 10.1136/bmjopen-2013-003150
                PMC ID: 3773632
                PubMed ID: 24002981
                SO-VID: b763ff26-7ea6-40ff-93df-3f455131cc99
                Copyright © Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions
                License:

                This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/

                History
                Date received : 2 May 2013
                Date revision received : 24 July 2013
                Date accepted : 26 July 2013
                Categories
                Subject: Gastroenterology and Hepatology
                Subject: Research
                Subject: 1506
                Subject: 1695
                Subject: 1697

                ScienceOpen disciplines: Medicine
                Keywords: gastroenterology,genetics
                Data availability:
                ScienceOpen disciplines: Medicine
                Keywords: gastroenterology, genetics

                Comments

                Comment on this article

                scite_

                Similar content451

                See all similar

                Cited by9

                See all cited by

                Most referenced authors649

                See all reference authors