湖南地区21-羟化酶缺乏症临床表型与基因型研究  

Analysis of clinical phenotype and genotype in patients with 21-hydroxylase deficiency in Hunan

作　　者：陶慧慧[1,2] 陈曦 谭新睿 李师君 张星星[1] Tao Huihui;Chen Xi;Tan Xinrui;Li Shijun;Zhang Xingxing(Department of Pediatrics,the Second Xiangya Hospital,Central South University,Changsha 410011,Hunan Province,China;Department of Pediatrics,the First Affiliated Hospital of University of South China,Hengyang 421001,Hunan Province,China)

机构地区：[1]中南大学湘雅二医院儿科,长沙410011 [2]南华大学附属第一医院儿科,湖南衡阳421001

出　　处：《中华实用儿科临床杂志》2020年第9期686-690,共5页Chinese Journal of Applied Clinical Pediatrics

摘　　要：目的:探究湖南地区21-羟化酶缺乏症基因突变特点及基因型与临床表型的关系。方法:收集2016年3月至2017年3月就诊于中南大学湘雅二医院儿科并确诊为21-羟化酶缺乏症的48例患儿,根据患儿的临床表现及生化特点,分为失盐型(SW)和单纯男性化型(SV)。采用Sanger测序和多重连接探针扩增技术(MLPA)检测CYP21A2基因突变,将基因诊断阳性者按突变严重程度分为重度突变组、中度突变组、未知突变组,探讨基因型与临床表型的关系。结果:1.在48例2-羟化酶缺乏症患儿中SW型28例,SV型20例。SW型初诊年龄明显小于SV型,差异有统计学意义(U=44.5,P<0.05),SW型患者肾上腺危象发生率高,SV型患者骨龄提前及性早熟发生率较高。2.CYP21A2基因异常阳性者44例,阳性率达91.7%,88个等位基因共检测到14种变异,分别为I2G、Del、I173N、R357W、R484fs(c.1451_1452delGGinsC、c.1450dupC)、R483fs、G111Vfs*21、Q319X、c.292+1G>A、c.377C>G、E6Cluster、p.H393Q、m.1647C>T,最常见的3种变异分别为I2G(36.4%)、I173N(20.4%)和Del(22.7%),其中p.H393Q、m.1647C>T为2种新发变异。SW型中最常见的变异为I2G(47.3%)和Del(27.3%);SV型中最常见的变异为I173N(48.5%)。3.重度突变组29例,其中SW型26例;中度突变组13例,其中SV型12例。重度突变组对SW型的预测值为89.7%,中度突变组对SV型的预测值为92.3%。结论:湖南地区21-羟化酶缺乏症的热点突变基因为I2G、I173N、Del,三者共占79.5%,重度突变组对SW型、中度突变组对SV型的预测值高,基因型与临床表型密切相关。Objective To investigate the clinical characteristic,gene mutations and genotype-phenotype correlation of 21-hydroxylase deficiency(21-OHD)in Hunan.Methods A total of 48 patients with 21-OHD who were admitted to the Department of Pediatrics,the Second Xiangya Hospital,Central South University from March 2016 to March 2017 were collected.According to the clinical manifestations and biochemical characteristics of the patients,they were divided into salt wasting(SW)and simple virilizing(SV).Sanger sequencing combined with multiplex ligation-dependent probe amplification(MLPA)were used to detect the mutations of CYP21A2 gene.The patients were divided into 3 groups according to their mutations severity:severe mutation group,moderate mutation group and unknown mutation group.Then,the correlation between genotype and phenotype was analyzed.Results(1)Forty-eight 21-OHD patients included 28 SW cases and 20 SV cases,and the first visiting age of SW was younger than that of SV,and the difference was statistically significant(U=44.5,P<0.05).The SW cases had high incidence rate of adrenal crisis and the SV patients were liable to advanced bone age and precocious puberty.(2)Forty-four patients were detected abnormal gene mutation and the positive rate of genetic diagnosis was 91.7%.Fourteen mutation types including I2G,Del,I173N,R357W,R484fs(c.1451_1452delGGinsC,c.1450dupC),R483fs,G111Vfs*21,Q319X,c.292+1G>A,c.377C>G,E6Cluster,p.H393Q and m.1647C>T,were found in 88 alleles.The most frequent mutations were I2G(36.4%),I173N(20.4%),and Del(22.7%).p.H393Q and m.1647C>T were 2 novel mutations.I2G(47.3%)and Del(27.3%)were the most frequent mutations in SW cases,and I173N(48.5%)was the most frequent mutation in SV cases.(3)Severe mutation was in 29 patients,including 26 SW,and moderate mutation was in 13 patients,including 12 SW.The percentage of SW in severe mutation group was 89.7%and SV in moderate mutation was 92.3%.Conclusions I2G,I173N and Del were the frequent mutations of 21-OHD in Hunan,and the total percen-tage was 79.5%.Ge

关 键 词：21-羟化酶缺乏症 基因型 临床表型 CYP21A2基因 

分 类 号：R725.8[医药卫生—儿科] R440[医药卫生—临床医学]