Trypsinogen copy number mutations in patients with idiopathic chronic pancreatitis
Trypsinogen copy number mutations in patients with idiopathic chronic pancreatitis
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DOI：
10.1016/j.cgh.2007.10.004
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发表时间：
2008-01-01
影响因子：
12.6
通讯作者：
Ferec, C.
中科院分区：
文献类型：
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作者：
Masson, E.;Le Marechal, C.;Ferec, C.
背景与目的我们最近报道了含有PRSS 1（编码阳离子型胰蛋白酶原）和PRSS 2（编码阴离子型胰蛋白酶原）基因的PGE 605胰蛋白酶片段的三重化导致遗传性胰腺炎。在此我们进一步研究这种拷贝数突变是否可以解释一些不明的法国白色特发性慢性胰腺炎（ICP）或家族性慢性胰腺炎（FCP）患者以及印度热带钙化性胰腺炎（TCP）患者。结果在该家系中发现了一个新的重复序列，202例ICP患者中，胰蛋白酶原基因位点的阳性率分别为10例和2例（发病年龄≤20岁），但在282名法国对照中不存在。此外，在1044例发病年龄>20岁的ICP患者中，有2例发现了重复突变。然而，2胰蛋白酶原的拷贝数突变，既没有观察到103 FCP患者，也没有268印度TCP patients.ConclusionsOur研究结果揭示了6%的年轻ICP患者的分子基础，并进一步证明，慢性胰腺炎是一种基因组疾病。我们的研究结果也增加了越来越多的证据表明，胰蛋白酶原基因突变似乎并没有发挥重要作用，在印度人口的TCP的发病机制。最后，这项研究的一个好处是，我们提供了令人信服的证据表明，所有5个先前描述的涉及PRSS 1或/和PRSS 2的拷贝数变异是人为因素。
Background & AimsWe have recently reported that the triplication of a ∼605 kilobase segment containing the PRSS1 (encoding cationic trypsinogen) and PRSS2 (encoding anionic trypsinogen) genes causes hereditary pancreatitis. Here we went further to investigate whether this copy number mutation could account for some unidentified French white patients with idiopathic chronic pancreatitis (ICP) or familial chronic pancreatitis (FCP) as well as Indian patients with tropical calcific pancreatitis (TCP).MethodsPatients and controls were screened by means of previously described quantitative fluorescent multiplex polymerase chain reaction and/or genotyping of the microsatellite marker rs3222967.ResultsThe ∼605 kilobase triplication and a novel duplication (confirmed by fluorescence in situ hybridization) of the trypsinogen locus were detected in 10 and 2 of 202 ICP patients, respectively (age of disease onset, ≤20 years) but were absent in 282 French controls. In addition, the duplication mutation was found in 2 of 1044 ICP patients whose age of disease onset was >20 years. However, the 2 trypsinogen copy number mutations were observed in neither 103 FCP patients nor 268 Indian TCP patients.ConclusionsOur findings revealed the molecular basis of 6% of the young ICP patients and further demonstrated that chronic pancreatitis is a genomic disorder. Our findings also add to the mounting evidence showing that trypsinogen gene mutations do not appear to play an important role in the pathogenesis of TCP in the Indian population. Finally, a dividend of this study is that we have provided convincing evidence to show that all 5 previously described copy number variations involving PRSS1 or/and PRSS2 are artifacts.