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Evidence for a common mutation in hereditary pancreatitis
S M Bell1, C Bennett, A F Markham
1Molecular Medicine Unit, University of Leeds, St James's University Hospital, UK.
Insights
A common mutation in the cationic trypsinogen gene causes hereditary pancreatitis, a disorder characterized by recurrent abdominal pain. This genetic alteration disrupts trypsin inactivation, leading to pancreatic autodigestion.
Area of Science:
- Genetics
- Gastroenterology
- Biochemistry
Background:
- Hereditary pancreatitis is an autosomal dominant disorder with incomplete penetrance.
- It presents with recurrent severe abdominal pain, often in childhood.
- A mutation in the cationic trypsinogen gene has been recently identified as a cause.
Purpose of the Study:
- To investigate the genetic basis of hereditary pancreatitis in a UK family.
- To determine if the previously identified mutation at residue 117 is common in hereditary pancreatitis.
Main Methods:
- Molecular analysis of the trypsinogen gene.
- Genetic sequencing to identify mutations.
Main Results:
- A G to A mutation at residue 117 of the trypsinogen gene was identified in the UK family.
- This is the same mutation previously found in US and Italian families.
Conclusions:
- The identified mutation at residue 117 is likely a common cause of hereditary pancreatitis.
- This mutation may disrupt trypsin inactivation, leading to pancreatic autodigestion.
Abstract:
Hereditary pancreatitis is an autosomal dominant disorder with incomplete penetrance. It is characterised by recurring episodes of severe abdominal pain and often presents in childhood. Recently, a mutation in the cationic trypsinogen gene was identified in this disease. Previously, only one mutation at residue 117 of the trypsinogen gene has been found in the five separate hereditary pancreatitis families, four from the USA and one from Italy. Alteration of the Arg117 site is believed to disrupt a fail-safe mechanism for the inactivation of trypsin, leading to autodigestion of the pancreas under certain conditions. Molecular analysis of the trypsinogen gene was carried out on a hereditary pancreatitis family from the UK. The same G to A mutation at residue 117 was identified in this family, suggesting that this is a common mutation in hereditary pancreatitis.