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The variable phenotype of the p.A16V mutation of cationic trypsinogen (PRSS1) in pancreatitis families
  1. Christopher J Grocock1,
  2. Vinciane Rebours2,
  3. Myriam Delhaye3,
  4. Ake Andren-Sandberg4,
  5. Frank U Weiss5,
  6. Roger Mountford6,
  7. Matthew Harcus1,
  8. Edyta Niemczyck1,
  9. Louis Vitone1,
  10. Susanna Dodd1,
  11. Maiken T Joergensen7,
  12. Rudolf W Ammann8,
  13. Ove Schaffalitzky de Muckadell9,
  14. Jane V Butler1,
  15. Philip Burgess10,
  16. Bronwyn Kerr11,
  17. Richard Charnley12,
  18. Robert Sutton1,
  19. Michael Raraty1,
  20. Jacques Deviere3,
  21. David Whitcomb13,
  22. John Neoptolemos1,
  23. Philippe Levy14,
  24. Markus M Lerch15,
  25. William Greenhalf1,*
  1. 1 The University of Liverpool, United Kingdom;
  2. 2 Hôpital Beaujon, France;
  3. 3 Erasme University Hospital, Belgium;
  4. 4 Karolinska University Hospital, Sweden;
  5. 5 Universitätsklinikum Greifswald, Germany;
  6. 6 Liverpool Women’s Hospital, United Kingdom;
  7. 7 The University of Liverpool, United States;
  8. 8 Odense University Hospital, Denmark;
  9. 9 University Hospital Zurich, Switzerland;
  10. 10 Odense University Hospita, Denmark;
  11. 11 Great Western Hospital, Swindon, United Kingdom;
  12. 12 St Mary’s Hospital, Manchester, United Kingdom;
  13. 13 Freeman Hospital, Newcastle upon Tyne, United Kingdom;
  14. 14 University of Pittsburgh, United States;
  15. 15 Hôpital Beaujon, Clichy, France;
  16. 16 Ernst-Moritz-Arndt Universität, Greifswald, Germany
  1. Correspondence to: William Greenhalf, The University of Liverpool, Division of Surgery and Oncology, Liverpool, L69 3GA, United Kingdom; greenhaf{at}


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 2 cases in 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: 5,25). There were 8 confirmed cases of exocrine failure, 4 of whom also had diabetes mellitus. There were 3 pancreatic cancer cases. Two of these were confirmed as p.A16V carriers, only one of whom was affected by pancreatitis. p.A16V pancreatitics 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 a multigenic inheritance of a predisposition to pancreatitis.

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