Commentaries

The true culprit within the SPINK1 p.N34S-containing haplotype is still at large

Jian-Min Chen^1,2,3,4, Claude Férec^1,2,3,4,5

¹ Institut National de la Santé et de la Recherche Médicale (INSERM), U613, Brest, France
² Etablissement Français du Sang (EFS)-Bretagne, Brest, France
³ Université de Bretagne Occidentale (UBO), Faculté de Médecine et des Sciences de la Santé, Brest, France
⁴ Institut Fédératif de Recherche (IFR) 148, Brest, France
⁵ Centre Hospitalier Universitaire (CHU) Brest, Hôpital Morvan, Laboratoire de Génétique Moléculaire et d’Histocompatibilité, Brest, France

Correspondence to:
Professor Claude Férec, INSERM U613-EFS-Bretagne-UBO, 46 rue Félix Le Dantec, 29218 Brest, France; Claude.Ferec@univ-brest.fr

The first 150 words of the full text of this article appear below.

Trypsinogen and other digestive zymogens are synthesised in the acinar cells of the exocrine pancreas. The serine protease inhibitor Kazal-type 1 (SPINK1), more commonly known as pancreatic secretory trypsin inhibitor (PSTI), is also synthesised in these cells. Because of its ability to inhibit approximately 20% of the potential trypsin activity within the pancreas, PSTI has long been thought to be one of the defensive mechanisms against a prematurely activated trypsin-driven digestive zymogen activation cascade leading to pancreatic autodigestion.¹ Given that gain-of-function missense mutations in the cationic trypsinogen gene (PRSS1) have been found to cause hereditary pancreatitis,^{2 3} SPINK1 was analysed by a candidate gene approach in 2000,^{4 5} and, since then, some 40 variants have been reported. In particular, 14 variants, all of which were exclusively found in chronic pancreatitis patients but not in controls, are clear or experimentally demonstrated loss-of-function mutations (table 1).^5–17 These findings support the . . . [Full text of this article]

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