Su Yueqing, Chen Hanqiang, Zhu Wenbin, Wang Jing, Zhou Jinfu, Chen Yao, Zhao Hong, Zeng Yinglin, Lin Feng, Zhang Honghua, Lin Qingying
Center of Neonatal Screening, Fujian Provincial Maternity and Children's Hospital of Fujian Medical University, Fuzhou, Fujian 350001, China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2016 Dec 10;33(6):786-791. doi: 10.3760/cma.j.issn.1003-9406.2016.06.009.
To assess the frequencies of CYP21A2 gene mutations among patients from Fujian area with classical 21-hydroxylase deficiency.
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.
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 CYP21A1P. 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).
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.
评估福建地区经典型21-羟化酶缺乏症患者中CYP21A2基因突变的频率。
对19例来自不同家族的经典型类固醇21-羟化酶缺乏症先证者及74名家庭成员，采用巢式聚合酶链反应、桑格测序和多重连接依赖探针扩增技术联合分析CYP21A2基因突变情况。采用时间分辨荧光免疫分析法检测所有家庭成员的17-羟孕酮（17-OHP）水平。分析先证者及其家庭成员的临床资料和实验室检查结果。
在19例先证者的38个等位基因中鉴定出11种突变。92.1%（35/38）的突变CYP21A2等位基因是由于CYP21A2与CYP21A1P之间的重组。分别在84.2%（32/38）和7.9%（3/38）的等位基因中鉴定出基因转换和缺失。IVS2-13A/C>G和嵌合体是最常见的突变，分别占所有突变等位基因的34.2%（13/38）和18.4%（7/38）。其中，IVS2+1G>A和Q318X+356W首次在中国报道。74.3%（55/74）的家庭成员为杂合突变携带者。然而，携带者与非携带者的17-OHP水平差异无统计学意义（P>0.05）。
福建地区似乎存在特定的CYP21A2基因突变谱，其中IVS2-13A/C>G和嵌合体是最常见的突变。
