Comprehensive screening for PRSS1, SPINK1, CFTR, CTRC and CLDN2 gene mutations in Chinese paediatric patients with idiopathic chronic pancreatitis: a cohort study.
Comprehensive screening for PRSS1, SPINK1, CFTR, CTRC and CLDN2 gene mutations in Chinese paediatric patients with idiopathic chronic pancreatitis: a cohort study.
复制标题
中国特发性慢性胰腺炎儿科患者PRSS1、SPINK1、CFTR、CTRC和CLDN2基因突变的综合筛查：一项队列研究。
DOI：
10.1136/bmjopen-2013-003150
复制
发表时间：
2013-09-03
期刊：
影响因子：
2.9
通讯作者：
Li ZS
中科院分区：
文献类型：
--
作者：
Wang W;Sun XT;Weng XL;Zhou DZ;Sun C;Xia T;Hu LH;Lai XW;Ye B;Liu MY;Jiang F;Gao J;Bo LM;Liu Y;Liao Z;Li ZS
遗传改变可能是中国年轻人慢性胰腺炎（CP）的原因之一。本研究旨在检测中国儿童特发性CP（ICP）的阳离子胰蛋白酶原（PRSS 1）、胰腺分泌型胰蛋白酶抑制剂或丝氨酸蛋白酶抑制剂Kazal 1型（SPINK 1）、囊性纤维化跨膜传导调节因子（CFTR）、糜蛋白酶C（CTRC）和CLDN 2基因的突变及其拷贝数变异（CNVs），探讨PRSS 1与ICP的关系。回顾展单一中心。75名ICP中国儿童（40名男孩和35名女孩）。PRSS 1、SPINK 1、CFTR、CTRC和CLDN 2基因的突变和CNV。7例患者存在PRSS 1杂合突变，即N29 I（n=1）、R122 H或R122 C（n=6）。5例患者PRSS 1基因的CNVs拷贝数异常（1拷贝4例，5拷贝1例）。43例患者在SPINK 1中具有IVS 3 + 2 T>C（rs 148954387）（10例纯合子和33例杂合子）。PRSS 1突变患者均未携带SPINK 1突变。PRSS 1和SPINK 1突变频率分别为9.3%和57.3%，总频率为66.6%（50/75）。此外，1例患者有CFTR的新缺失（从c.500到c.508的GCTTCCTA通过终止密码子导致缩短的多肽分子）。另一名患者在CLDN 2外显子2中存在新的错义（c.592A>C突变）。临床上，SPINK 1基因突变患者的胰管结石、胰腺假性囊肿和胰腺钙化发生率高于SPINK 1基因突变阴性患者（p<0.05）。SPINK 1基因突变与中国ICP儿童相关性更高。SPINK 1 IVS 3 + 2 T>C突变可能在中国儿童ICP发病中起重要作用。然而，这些基因在中国ICP发生发展中的作用还需要进一步的研究。
Genetic alterations may contribute to chronic pancreatitis (CP) in Chinese young patients. This study was designed to investigate mutations of cationic trypsinogen (PRSS1), pancreatic secretory trypsin inhibitor or serine protease inhibitor Kazal type 1 (SPINK1), cystic fibrosis transmembrane conductance regulator (CFTR), chymotrypsin C (CTRC) and CLDN2 genes and the copy number variations (CNVs) of PRSS1 and asses associations with the development of idiopathic CP (ICP) in Chinese children. Retrospective. A single center. 75 ICP Chinese children (40 boys and 35 girls). Mutations of PRSS1, SPINK1, CFTR, CTRC and CLDN2 genes and CNVs. 7 patients had heterozygous mutations in PRSS1, that is, N29I (n=1), R122H or R122C (n=6). The CNVs of PRSS1 in five patients had abnormal copies (1 copy (n=4), five copies (n=1)). 43 patients had IVS3+2T>C (rs148954387) (10 homozygous and 33 heterozygous) in SPINK1. None of the PRSS1 mutation patients carried a SPINK1 mutation. Frequency of PRSS1 and SPINK1 mutations was 9.3% and 57.3%, respectively, with an overall frequency of 66.6% (50/75). In addition, one patient had a novel deletion of CFTR (GCTTCCTA from c.500 to c.508 leading to the shortened polypeptide molecule via a stop codon). Another patient had a novel missense in CLDN2 exon 2 (c.592A>C mutation). Clinically, patients with SPINK1 mutations had a higher rate of pancreatic duct stones, pancreatic pseudocyst and pancreatic calcification than those without SPINK1 mutations (p<0.05). SPINK1 mutations were more commonly associated with Chinese children with ICP. SPINK1 IVS3+2T>C mutation may play an important role in the pathogenesis of Chinese paediatric ICP. However, further study is needed to confirm and to investigate the role of these genes in the development of Chinese ICP.
登录
查看更多内容
影响因子：
29.4
作者：
Schneider A;Larusch J;Sun X;Aloe A;Lamb J;Hawes R;Cotton P;Brand RE;Anderson MA;Money ME;Banks PA;Lewis MD;Baillie J;Sherman S;Disario J;Burton FR;Gardner TB;Amann ST;Gelrud A;George R;Rockacy MJ;Kassabian S;Martinson J;Slivka A;Yadav D;Oruc N;Barmada MM;Frizzell R;Whitcomb DC
通讯作者：
Whitcomb DC
影响因子：
2
作者：
Nam, MH;Hijikata, M;Keicho, N
通讯作者：
Keicho, N
影响因子：
56.9
作者：
Sebat, J;Lakshmi, B;Wigler, M
通讯作者：
Wigler, M
影响因子：
158.5
作者：
Sharer, N;Schwarz, M;Braganza, J
通讯作者：
Braganza, J
影响因子：
4
作者：
Fujiki, K;Ishiguro, H;Naruse, S
通讯作者：
Naruse, S