Identification of CFTR, PRSS1, and SPINK1 mutations in 381 patients with pancreatitis
Identification of CFTR, PRSS1, and SPINK1 mutations in 381 patients with pancreatitis
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DOI：
10.1097/01.mpa.0000232014.94974.75
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发表时间：
2006-10-01
期刊：
影响因子：
2.9
通讯作者：
Kammesheidt, Anja
中科院分区：
文献类型：
--
作者：
Keiles, Steven;Kammesheidt, Anja
目的：慢性胰腺炎是一种进行性炎症性疾病，导致不可逆的外分泌和/或内分泌损害。阳离子胰蛋白酶原(PRSS1)基因突变可引起遗传性胰腺炎。方法：我们对381例初诊为慢性或复发性胰腺炎的患者进行了分析，以获得CFTR、SPINK1和PRSS1基因的全面遗传信息。结果：在166个突变的CFTR等位基因中，有32%(122/381)的患者被鉴定，其中包括12个新的CFTR变异：4375-20A&gT；G，F575Y，K598E，L1260P，G194R，F834L，S573C，2789+17，C>；621+83A>；在122例CFTR突变患者中，5.5%(21/381)同时携带SPINK1突变，1.8%(7/381)同时携带PRSS1突变。此外，8.9%(34/381)的患者有不同的SPINK1突变。另有6.3%(24/381)的患者存在8种不同的PRSS1突变。更有甚者。1.3%(5/381)的患者存在I PRSS1和I SPINK1突变。共有49%(185/381)的患者携带一个或多个突变。结论：对CFTR、PRSS1和SPINK1基因的综合检测发现，在他们的医生认为适合进行基因检测的所有受试者中，有近一半的人存在基因变异。综合测试确定了许多标准临床筛查小组无法识别的新变种。
Objectives: Chronic pancreatitis is a progressive inflammatory disorder leading to irreversible exocrine and/or endocrine impairment. It is well documented that mutations in the cationic trypsinogen (PRSS1) gene can cause hereditary pancreatitis. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) and the serine protease inhibitor Kazal type I (SPINK1) genes are also associated with pancreatitis.Methods: We analyzed 381 patients with a primary diagnosis of chronic or recurrent pancreatitis using the Ambry Test: Pancreatitis to obtain comprehensive genetic information for the CFTR, SPINK1, and PRSS1 genes.Results: The results identified 32% (122/381) of patients with 166 mutant CFTR alleles, including 12 novel CFTR variants: 4375-20 A > G, F575Y, K598E, L1260P, G194R, F834L, S573C, 2789+17 C,>, 621+83 A > G, T164S, 621+25 A > G, and 3500-19 G > A. Of 122 patients with CFTR mutations, 5.5% (21/381) also carried a SPINK1 mutation, and 1.8% (7/381) carried a PRSS1 mutation. In addition, 8.9% (34/381) of all patients had I of I I different SPINK1 mutations. Another 6.3% (24/381) of the patients had I of 8 different PRSS1 mutations. Moreover. 1.3% of the patients (5/381) had I PRSS1 and I SPINK1 mutation. A total 49% (185/381) of the patients carried one or more mutations.Conclusions: Comprehensive testing of the CFTR, PRSS1, and SPINK1 genes identified genetic variants in nearly half of all subjects considered by their physicians as candidates for genetic testing. Comprehensive test identified numerous novel variants that would not be identified by standard clinical screening panels.