Witt H, Luck W, Hennies H C, Classen M, Kage A, Lass U, Landt O, Becker M
Department of Pediatrics, Charité, Campus Virchow-Klinikum, Humboldt University, Berlin, Germany.
Nat Genet. 2000 Jun;25(2):213-6. doi: 10.1038/76088.
Chronic pancreatitis (CP) is a continuing or relapsing inflammatory disease of the pancreas. In approximately one-third of all cases, no aetiological factor can be found, and these patients are classified as having idiopathic disease. Pathophysiologically, autodigestion and inflammation may be caused by either increased proteolytic activity or decreased protease inhibition. Several studies have demonstrated mutations in the cationic trypsinogen gene (PRSS1) in patients with hereditary or idiopathic CP. It is thought that these mutations result in increased trypsin activity within the pancreatic parenchyma. Most patients with idiopathic or hereditary CP, however, do not have mutations in PRSS1 (ref. 4). Here we analysed 96 unrelated children and adolescents with CP for mutations in the gene encoding the serine protease inhibitor, Kazal type 1 (SPINK1), a pancreatic trypsin inhibitor. We found mutations in 23% of the patients. In 18 patients, 6 of whom were homozygous, we detected a missense mutation of codon 34 (N34S). We also found four other sequence variants. Our results indicate that mutations in SPINK1 are associated with chronic pancreatitis.
慢性胰腺炎（CP）是一种胰腺的持续性或复发性炎症性疾病。在所有病例中，约三分之一找不到病因，这些患者被归类为患有特发性疾病。在病理生理学上，自消化和炎症可能是由蛋白水解活性增加或蛋白酶抑制作用降低引起的。多项研究已证实，遗传性或特发性慢性胰腺炎患者的阳离子胰蛋白酶原基因（PRSS1）存在突变。据认为，这些突变会导致胰腺实质内胰蛋白酶活性增加。然而，大多数特发性或遗传性慢性胰腺炎患者的PRSS1没有突变（参考文献4）。在此，我们分析了96名无关的慢性胰腺炎儿童和青少年，以寻找编码丝氨酸蛋白酶抑制剂Kazal 1型（SPINK1，一种胰腺胰蛋白酶抑制剂）的基因突变情况。我们在23%的患者中发现了突变。在18名患者中，其中6名是纯合子，我们检测到第34密码子的错义突变（N34S）。我们还发现了其他四个序列变异。我们的结果表明，SPINK1突变与慢性胰腺炎有关。
