Gut · 2009
The variable phenotype of the p.A16V mutation of cationic trypsinogen (PRSS1) in pancreatitis families.
СтатьяМногоцентровое исследованиеПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Grocock Christopher J, Rebours Vinciane, Delhaye Myriam N, Andrén-Sandberg Ake, Weiss Frank Ulrich, Mountford Roger, Harcus Matthew J, Niemczyck Edyta, Vitone Louis J, Dodd Susanna, Jørgensen Maiken Thyregod, Ammann Rudolf W, Schaffalitzky de Muckadell Ove, Butler Jane V, Burgess Phillip, Kerr Bronwyn, Charnley Richard, Sutton Robert, Raraty Michael G, Devière Jacques, Whitcomb David C, Neoptolemos John P, Lévy Philippe, Lerch Markus M, Greenhalf William, European Registry of Hereditary Pancreatitis and Pancreatic Cancer
Аннотация
OBJECTIVE: To characterise the phenotypes associated with the p.A16V mutation of PRSS1.
DESIGN: Clinical and epidemiological data were collected for any family in which a p.A16V mutation was identified, either referred directly to the European Registry of Hereditary Pancreatitis and Familial Pancreatic Cancer or via a collaborator. DNA samples were tested for mutations in PRSS1, SPINK1, CFTR and CTRC.
PATIENTS: Participants were recruited on the basis of either family history of pancreatitis (acute or chronic) or the results of genetic testing. Families were categorised as having hereditary pancreatitis (HP), idiopathic disease or pancreatitis in a single generation. HP was defined as >or=2 cases in >or=2 generations. Main outcome measures Onset of painful episodes of pancreatitis, death from pancreatic cancer, diagnosis of diabetes mellitus and exocrine pancreatic failure.
RESULTS: Ten families with p.A16V mutations were identified (22 affected individuals): six HP families, three with idiopathic disease and one with only a single generation affected. The median age of onset, ignoring non-penetrants, was 10 years (95% CI 5 to 25). There were eight confirmed cases of exocrine failure, four of whom also had diabetes mellitus. There were three pancreatic cancer cases. Two of these were confirmed as p.A16V carriers, only one of whom was affected by pancreatitis. Those with p.A16V pancreatitis were compared to affected individuals with p.R122H, p.N29I and no PRSS1 mutation. No significant differences were proven using logrank or Mann-Whitney U tests.
CONCLUSIONS: Penetrance of p.A16V is highly variable and family dependent, suggesting it contributes to multigenic inheritance of a predisposition to pancreatitis.
DESIGN: Clinical and epidemiological data were collected for any family in which a p.A16V mutation was identified, either referred directly to the European Registry of Hereditary Pancreatitis and Familial Pancreatic Cancer or via a collaborator. DNA samples were tested for mutations in PRSS1, SPINK1, CFTR and CTRC.
PATIENTS: Participants were recruited on the basis of either family history of pancreatitis (acute or chronic) or the results of genetic testing. Families were categorised as having hereditary pancreatitis (HP), idiopathic disease or pancreatitis in a single generation. HP was defined as >or=2 cases in >or=2 generations. Main outcome measures Onset of painful episodes of pancreatitis, death from pancreatic cancer, diagnosis of diabetes mellitus and exocrine pancreatic failure.
RESULTS: Ten families with p.A16V mutations were identified (22 affected individuals): six HP families, three with idiopathic disease and one with only a single generation affected. The median age of onset, ignoring non-penetrants, was 10 years (95% CI 5 to 25). There were eight confirmed cases of exocrine failure, four of whom also had diabetes mellitus. There were three pancreatic cancer cases. Two of these were confirmed as p.A16V carriers, only one of whom was affected by pancreatitis. Those with p.A16V pancreatitis were compared to affected individuals with p.R122H, p.N29I and no PRSS1 mutation. No significant differences were proven using logrank or Mann-Whitney U tests.
CONCLUSIONS: Penetrance of p.A16V is highly variable and family dependent, suggesting it contributes to multigenic inheritance of a predisposition to pancreatitis.
Предметные рубрики MeSH
AdolescentAdultAge of OnsetCarrier ProteinsChildChild, PreschoolCystic Fibrosis Transmembrane Conductance RegulatorFemaleGenetic Predisposition to DiseaseHeterozygoteHumansInfantMaleMiddle AgedMutationNeoplasm ProteinsPancreatic NeoplasmsPancreatitisPedigreePenetranceTrypsinTrypsin Inhibitor, Kazal PancreaticYoung Adult