河南地区21-羟化酶缺乏症患儿CYP21A2基因突变谱分析  

Mutation analysis of CYP21A2 gene in children with 21-hydroxylase deficiency in Henan

作　　者：杨海花[1] 王会贞[1] 陈永兴 王小红[1] 杨威[1] 陈琼[1] 沈凌花 刘晓景 卫海燕[1] YANG Haihua;WANG Huizhen;CHEN Yongxing;WANG Xiaohong;YANG Wei;CHEN Qiong;SHEN Linghua;LIU Xiaojing;WEI Haiyan(Children’s Hospital Affiliated to Zhengzhou University;Henan Children’s Hospital;Zhengzhou Children’s Hospital,Zhengzhou 450000,Henan,China)

机构地区：[1]郑州大学附属儿童医院,河南省儿童医院,郑州儿童医院,河南郑州450000

出　　处：《临床儿科杂志》2018年第10期756-760,共5页Journal of Clinical Pediatrics

摘　　要：目的探讨河南地区21羟化酶缺乏症(21-OHD)遗传特征。方法回顾分析2009—2016年,祖籍河南,汉族,临床诊断为21-OHD患儿及其家系的基因检测结果。应用Sanger测序和MLPA方法进行21羟化酶基因CYP21A2检测,对于CYP21A2基因突变呈阴性的患儿,再进行二代测序以明确诊断。结果共54个家系55例患儿,病程1个月～8年,其中临床诊断失盐型49例(男37例、女12例),单纯男性化型6例(女3例、男3例)。46例患儿检测到CYP21A2基因突变,突变频率依次为c.293-13A/C>G(I2G)、全基因缺失或大片段缺失、C.955G>T(p.Q319X)、C.515T>A (p.I172N)、c.1069G>T(p.R357W)。9例CYP21A2检测阴性者,二代测序检测到NROB1(DAX1)7例,更正诊断为先天性肾上腺发育不良。结论河南地区临床诊断21-OHD患儿CYP21A2最常见热点突变类型是c.293-13A/C>G(I2G),其次为基因大片段缺失。Objective To explore the genetic characteristics of 21 hydroxylase deficiency(21-OHD)in Henan area.Methods The genetic test results of 21-OHD children and their families of Han nationality originally from Henan province were retrospectively analyzed from 2009 to 2016.Sanger sequencing and multiplex ligation-dependent probe amplification(MLPA)methods were performed to detect mutations in CYP21A2 gene.For children with negative mutation of CYP21A2 gene,next generation sequencing(NGS)was performed to confirm the diagnosis.Results A total of 55 patients from 54 families with a disease course of one month to 8 years were studied.There were 49 cases(37 boys and 12 girls)of clinically diagnosed salt wasting(SW)type and 6 cases(3 boys and 3 girls)of simple virilizing(SV)type.The CYP21A2 gene mutation was detected in 46 children,and the most frequent mutation identified was c.293-13A/C>G(I2G),followed by partial or complete deletion of the gene,c.955G>T(p.Q319X),c.515T>A(p.I172N)and c.1069G>T(p.R357W).Among 9 children with negative CYP21A2,there were 7 children whose diagnosis was corrected to congenital adrenal dysplasia due to positive NROB1(DAX1)mutations detected by NGS analysis.Conclusions The most common mutation type of CYP21A2 in children diagnosed with 21-OHD clinically in Henan is c.293-13a/c>G(I2G),followed by the large fragment deletion of the gene.

关 键 词：21羟化酶缺乏症 CYP21A2 基因突变 先天性肾上腺皮质增生症 

分 类 号：R725.8[医药卫生—儿科]