Hereditary pancreatitis is caused by a mutation in the cationic trypsinogen gene View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1996-10

AUTHORS

David C. Whitcomb, Michael C. Gorry, Robert A. Preston, William Furey, Michael J. Sossenheimer, Charles D. Ulrich, Stephen P. Martin, Lawrence K. Gates, Stephen T. Amann, Phillip P. Toskes, Roger Liddle, Kevin McGrath, G. Uomo, J. C. Post, Garth D. Ehrlich

ABSTRACT

Hereditary pancreatitis (HP) is a rare, early-onset genetic disorder characterized by epigastric pain and often more serious complications. We now report that an Arg–His substitution at residue 117 of the cationic trypsinogen gene is associated with the HP phenotype. This mutation was observed in all HP affected individuals and obligate carriers from five kindreds, but not in individuals who married into the families nor in 140 unrelated individuals. X-ray crystal structure analysis, molecular modelling, and protein digest data indicate that the Arg 117 residue is a trypsin-sensitive site. Cleavage at this site is probably part of a fail-safe mechanism by which trypsin, which is activated within the pancreas, may be inactivated; loss of this cleavage site would permit autodigestion resulting in pancreatitis. More... »

PAGES

141-145

References to SciGraph publications

Journal

TITLE

Nature Genetics

ISSUE

2

VOLUME

14

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ng1096-141

DOI

http://dx.doi.org/10.1038/ng1096-141

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1012686614

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/8841182


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40 cationic trypsinogen gene
41 cleavage site
42 complications
43 crystal structure analysis
44 data
45 digest data
46 disorders
47 early-onset genetic disorders
48 epigastric pain
49 fail-safe mechanism
50 family
51 genes
52 genetic disorders
53 hereditary pancreatitis
54 individuals
55 kindreds
56 loss
57 mechanism
58 modelling
59 molecular modelling
60 mutations
61 obligate carriers
62 pain
63 pancreas
64 pancreatitis
65 part
66 phenotype
67 residue 117
68 residues
69 serious complications
70 sites
71 structure analysis
72 substitution
73 trypsin
74 trypsin-sensitive sites
75 trypsinogen gene
76 unrelated individuals
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