Rapid CommunicationsA signal peptide cleavage site mutation in the cationic trypsinogen gene is strongly associated with chronic pancreatitis☆
Section snippets
Participants
Forty-four unrelated children and adolescents with CP and 56 first-degree relatives were enrolled for genetic analysis. All patients were white. CP was arbitrarily defined as a condition characterized by at least two clearly separated episodes of recurring abdominal pain, increase in serum lipase and/or amylase levels, and pathological sonographic findings. This definition was necessary because the recently revised and simplified classification of pancreatitis in acute pancreatitis and CP is
Results
Analysis of the complete coding region of the cationic trypsinogen gene revealed mutations in 5 of 44 patients: an altered migration of PCR products of exon 2 was detected in 4 patients by SSCP analysis. DNA sequencing identified a heterozygous C to T transition at position 131906 of the DNA sequence according to Rowen et al.11 This substitution leads to a missense mutation at codon 16 by exchange of an alanine residue by valine (GCCb → GTC, A16V; numbering of amino acids begins at the
Discussion
To our knowledge this is the first study to determine the frequency of mutations in the cationic trypsinogen gene in unrelated patients with CP. In contrast, previous studies focusing exclusively on hereditary pancreatitis included families with several affected members. Because predisposing factors such as alcohol abuse are uncommon in children and adolescents, this age group was thought to be suitable for a prevalence study of genetic defects of cationic trypsinogen.
In 4 of 44 patients, we
Acknowledgements
The authors thank the members of the Gesellschaft für Pädiatrische Gastroenterologie und Ernährung (GPGE) for providing samples.
References (13)
- et al.
Report of the Second International Symposium on the Classification of Pancreatitis in Marseille, France, March 28–30, 1984
Gastroenterology
(1985) - et al.
Pedigree of a family with hereditary chronic relapsing pancreatitis
Gastroenterology
(1952) - et al.
A gene for hereditary pancreatitis maps to chromosome 7q35
Gastroenterology
(1996) - et al.
Linkage studies in a large kindred with hereditary pancreatitis confirms mapping of the gene to a 16-cM region on 7q
Genomics
(1996) - et al.
Mutations in the cationic trypsinogen gene are associated with recurrent acute and chronic pancreatitis
Gastroenterology
(1997) - et al.
The cell biology of experimental pancreatitis
N Engl J Med
(1987)
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Address requests for reprints to: Heiko Witt, M.D., Kinderklinik, Charité/Campus Virchow-Klinikum, Humboldt-Universität, Augustenburger Platz 1, 13353 Berlin, Germany. e-mail: [email protected]; fax: (49) 30-450-66917.