Hereditary pancreatitis caused by triplication of the trypsinogen locus

Cédric Le Maréchal^{1, 2, 3, 4, 7}, Emmanuelle Masson^1, 2, 7, Jian-Min Chen^1, 2, 4, Frédéric Morel^2, 5, Philippe Ruszniewski⁶, Philippe Levy⁶ & Claude Férec^{1, 2, 3, 4}

¹  Institut National de la Santé et de la Recherche Médicale (INSERM), U613, 29220 Brest, France.

²  Université de Bretagne Occidentale, Faculté de Médecine de Brest et des Sciences de la Santé, 29238 Brest, France.

³  Centre Hospitalier Universitaire (CHU) Brest, Hôpital Morvan, Laboratoire de Génétique Moléculaire et d'Histocompatibilité, 29220 Brest, France.

⁴  Etablissement Français du Sang–Bretagne, 29220 Brest, France.

⁵  CHRU Brest, Hôpital Morvan, Service de Cytogénétique, Cytologie et Biologie de la Reproduction, 29238 Brest, France.

⁶  Pôle des Maladies de l'Appareil Digestif, Hôpital Beaujon, Assistance Publique-Hopitaux de Paris, 92118 Clichy, France.

⁷  These authors contributed equally to this work.

Hereditary pancreatitis has been reported to be caused by 'gain-of-function' missense mutations in the cationic trypsinogen gene (PRSS1). Here we report the triplication of a 605-kb segment containing the PRSS1 gene on chromosome 7 in five families with hereditary pancreatitis. This triplication, which seems to result in a gain of trypsin through a gene dosage effect, represents a previously unknown molecular mechanism causing hereditary pancreatitis.

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