经典型21-羟化酶缺乏症的CYP21A2基因突变分析  

Analysis of CYP21A2 gene mutations among patients with classical steroid 21-hydroxylase deficiency

作　　者：苏跃青[1] 陈涵强[2] 朱文斌[1] 王旌[1] 周进福[1] 陈瑶[1] 赵红[1] 曾颖琳[1] 林枫[1] 张洪华[1] 林庆颖[1] 

机构地区：[1]福建医科大学附属福建省妇幼保健院新生儿疾病筛查中心,福州350001 [2]福建医科大学附属福建省妇幼保健院新生儿科,福州350001

出　　处：《中华医学遗传学杂志》2016年第6期786-791,共6页Chinese Journal of Medical Genetics

基　　金：福建省自然科学基金（2016J01489）

摘　　要：目的探讨福建地区经典型21-羟化酶缺乏症患者CYP21A2基因的突变特征及CYP21A2基因突变谱系。方法应用巢式PCR、基因测序和多重连接探针扩增技术分析19例经典型21-羟化酶缺乏症先证者及74名家系成员CYP21A2基因的突变；用时间分辨荧光分析法检测74名家系成员的血17-羟孕酮浓度。结果在19例先证者中，发现11种源于父母的致病性突变；其中92．1％（35／38）等位基因突变与21-羟化酶真假基因重组有关，包括84．2％（32／38）的真假基因间碱基互换，7．9％（3／38）CYP21A2基因大片段缺失；IVS2-13A／C＞G和真假基因融合为最常见2种突变类型，分别占34．2％（13／38）和18．4％（7／38）；IVs2＋1G＞A和Q318X＋356W突变为国内首次报道。74名家系成员中，74．3％（55／74）为CYP21A2基因致病突变携带者，25．7％（19／74）为非携带者；携带者与非携带者的17-羟孕酮浓度值分别为8．1±3．2nmol／L与5．2±3．7nmol／L，差异无统计学意义（P＞0．05）。结论福建地区经典型21-羟化酶缺乏症患者CYP21A2基因具有独特的突变特征，IVS2-13A／C＞G和真假基因融合为两种最常见的突变。Objective To assess the frequencies of CYP21A2 gene mutations among patients from Fujian area with classical 21-hydroxylase deficiency. Methods For 19 probands from different families affected with classical steroid 21 hydroxylase deficiency and 74 family members, mutations of the CYP21A2 gene were analyzed with combined nested polymerase chain reaction, Sanger sequencing and multiplex ligation-dependent probe amplification. Time resolved fluorescence immunoassay was performed to determine the level of 17-hydroxyprogesterone （17-OHP） in all family members. Clinical data and laboratory results of the probands and their family members were analyzed. Results Eleven mutations were identified among the 38 alleles from the 19 probands. 92. 1% （35/38） of the mutant CYP21A2 alleles were due to recombination between CYP21A2 and CYP21AIP. Gene conversion and deletions were identified in 84.2% （32/38） and 7. 9% （3/38） of the alleles, respectively. IVS2 13A/C〉 G and chimeras were the most common mutations, which respectively accounted for 34. 2% （13/38） and 18. 4% （7/38） of all mutant alleles. Among these, IVS2＋1G〉A and Q318X＋356W were first reported in China. 74.3% （55/74） of the family members were carriers of heterozygous mutations. However, no significant difference was found in the 17-OHP levels between carriers and non-carriers （P〉0. 05）. Conclusion There seems to be a specific spectrum of CYP21A2 gene mutations in Fujian area, where IVS2-13A/C〉G and chimeras are the most common mutations.

关 键 词：经典型21-羟化酶症 基因突变 巢式PCR 基因测序 多重连接探针扩增技术 

分 类 号：R5[医药卫生—内科学]