Teich Niels, Rosendahl Jonas, Tóth Miklós, Mössner Joachim, Sahin-Tóth Miklós
Medizinische Klinik und Poliklinik II, Universität Leipzig, Germany.
Hum Mutat. 2006 Aug;27(8):721-30. doi: 10.1002/humu.20343.
Ten years ago, the groundwork for the discovery of the genetic basis of chronic pancreatitis was laid by linkage analyses of large kindreds with autosomal dominant hereditary chronic pancreatitis. Subsequent candidate gene sequencing of the 7q35 chromosome region revealed a strong association of the c.365G > A (p.R122 H) mutation of the PRSS1 gene encoding cationic trypsinogen with hereditary pancreatitis. In the following years, further mutations of this gene were discovered in patients with hereditary or idiopathic chronic pancreatitis. In vitro the mutations increase autocatalytic conversion of trypsinogen to active trypsin and thus probably cause premature, intrapancreatic trypsinogen activation in vivo. The clinical presentation is highly variable, but most affected mutation carriers have relatively mild disease. In this review, we summarize the current knowledge on trypsinogen mutations and their role in pancreatic diseases.
十年前，通过对常染色体显性遗传性慢性胰腺炎的大型家族进行连锁分析，为发现慢性胰腺炎的遗传基础奠定了基础。随后对7q35染色体区域进行候选基因测序，结果显示，编码阳离子胰蛋白酶原的PRSS1基因的c.365G > A (p.R122 H) 突变与遗传性胰腺炎密切相关。在接下来的几年里，在遗传性或特发性慢性胰腺炎患者中发现了该基因的更多突变。在体外，这些突变会增加胰蛋白酶原向活性胰蛋白酶的自身催化转化，因此可能在体内导致胰蛋白酶原过早地在胰腺内激活。临床表现差异很大，但大多数受影响的突变携带者病情相对较轻。在这篇综述中，我们总结了目前关于胰蛋白酶原突变及其在胰腺疾病中作用的知识。
