PRSS1和SPINK1基因热点突变检测对遗传性胰腺炎高危人群的诊断价值  

DIAGNOSTIC VALUE OF HOT SPOT MUTATION DETECTION OF PRSS1 AND SPINK1 GENES IN HIGH-RISK POPULATIONS OF HEREDITARY PANCREATITIS

作　　者：张文清 雷珂[2] 魏宏云 王彩霞[3] 王玲珍[3] 陈志红[3] 李晓宇[1] ZHANG Wenqing;LEI Ke;WEI Hongyun;WANG Caixia;WANG Lingzhen;CHEN Zhihong;LI Xiaoyu(Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao 266003, China)

机构地区：[1]青岛大学附属医院消化内科,山东青岛2660031 [2]青岛大学附属医院医学研究中心,肿瘤免疫及细胞治疗中心,山东青岛2660031 [3]青岛大学附属医院儿童医学中心,山东青岛2660031

出　　处：《精准医学杂志》2022年第2期157-160,共4页Journal of Precision Medicine

基　　金：国家自然科学基金青年基金(81802777)。

摘　　要：目的探讨人阳离子胰蛋白酶原(PRSS1)基因和丝氨酸蛋白酶抑制剂Kazal 1型(SPINK1)基因热点突变检测对遗传性胰腺炎(hereditary pancreatitis,HP)高危人群的诊断价值。方法采集2020年8月—2021年9月我院住院的高危HP患者的外周静脉血,提取标本DNA,进行PCR扩增,利用Sanger测序法检测HP高危患者外周血PRSS1和SPINK1基因的突变情况。对于测序中发现的非热点突变,以慢性胰腺炎遗传风险因素数据库中已知致病突变和可能致病突变认定为HP相关突变,数据库中未有的突变,在PubMed数据库和ClinVar数据库中查找是否有突变相关报道和致病性分析结果。结果6例患者中5例检测到突变,3例患者检测到PRSS1基因杂合性突变,分别为热点突变c.364 C>T和非热点突变c.455-33 C>T、c.235 G>A,其中c.455-33 C>T突变未见报道,c.235 G>A突变首次在中国人群中报道;2例患者检测到SPINK1杂合性突变,均为c.194+2 T>C突变。结论PRSS1和SPINK1基因热点突变检测对HP高危人群具有较高的诊断价值,适合在HP高危人群中大规模筛查,有利于HP患者精准诊断和早期干预。Objective To investigate the diagnostic value of hot spot mutation detection of human cationic trypsinogen(PRSS1)gene and serine peptidase inhibitor Kazal type 1(SPINK1)gene in high-risk populations of hereditary pancreatitis(HP).Methods Peripheral venous blood was collected from high-risk HP patients hospitalized in our hospital from August 2020 to September 2021.DNA was extracted for PCR amplification,and Sanger sequencing was used to detect the mutations of PRSS1 and SPINK1.For non-hot spot mutations found in sequencing,the known and potential pathogenic mutations in the chronic pancreatitis genetic risk factor database were used to identify HP-related mutations,and the mutations absent in the database were searched for in the PubMed database and ClinVar database for reported mutations and pathogenicity analysis.Results Mutations were detected in 5 of the 6 patients,and heterozygous mutations in the PRSS1 gene were detected in 3 patients,namely hot spot mutation c.364 C>T and non-hot spot mutations c.455-33 C>T and c.235 G>A.The c.455-33 C>T mutation had not been reported,and the c.235 G>A mutation was reported in the Chinese population for the first time.A SPINK1 heterozygous mutation c.194+2 T>C was detected in 2 patients.Conclusion PRSS1 and SPINK1 gene hotspot mutation detection is highly valuable for diagnosis of populations at high risk of HP and suitable for large-scale screening,which can be used in accurate diagnosis and early intervention of HP patients.

关 键 词：胰腺炎 胰蛋白酶原 丝氨酸蛋白酶抑制剂 基因检测 突变 DNA突变分析 诊断 

分 类 号：R567[医药卫生—呼吸系统] R394[医药卫生—内科学]