Abstract: Objective To analyze CYP21A2 mutations in 21-hydroxylase deficiency children and their parents,and to provide scientific evidence for effectively performing prenatal diagnosis. Methods Fourteen 21-hydroxylase deficiency patients and the parents from Liuzhou Municipal Maternity and Child Healthcare Hospital were enrolled from August 2013 to December 2015.The mutations of CYP21A2 and gross deletions were determined by PCR based Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA). Results Genetic analysis revealed 4 kinds of CYP21A2 mutations.Different forms of point mutations accounted for 89.3% (25/28),including c.293-13C>G (46.4%),c.518T>A (39.2%),and c.737delA (3.6%).Deletions accounted for 10.7% (3/28),all of which were CYP21A2 exon 1-3 deletion.Prenatal diagnosis revealed 2 cases were carriers. Conclusions CYP21A2 c.293-13C>G and c.518T>A are common mutations in local patients with 21-hydroxylase deficiency.Sanger sequencing combined with MLPA could identify both point mutation and deletions of CYP21A2,which may be a reliable method for molecular diagnosis of CAH.

Key words: congenital adrenal hyperplasia, CYP21A2, point mutation, deletion

摘要： 目的 对21-羟化酶缺乏症患儿及其父母的CYP21A2基因进行突变分析,为能有效进行产前诊断提供科学依据。方法 收集2013年8月-2015年12月就诊于柳州市妇幼保健院的14例21-羟化酶缺乏症患儿及其父母外周血,提取基因组DNA,采用Sanger测序及多重连接探针扩增技术(MLPA)分析CYP21A2基因的所有外显子及其两端侧翼序列,并通过父母的基因型进行验证,以此为依据进行胎儿的产前诊断。结果 14例先证者中共检出4种突变,不同形式的点突变占89.3%(25/28),分别为c.293-13C>G(46.4%)、c.518T>A(39.2%)、c.737delA(3.6%),缺失突变占10.7%,均为CYP21A2基因外显子1-3缺失。2例产前诊断胎儿均为携带者。结论 CYP21A2基因突变位点c.293-13C>G及c.518T>A是本地区21-羟化酶缺乏症的常见突变。Sanger测序联合多重连接探针扩增技术可以同时检测出CYP21A2基因的点突变和缺失突变,为疾病的确诊与临床表型的判断提供了可靠依据。

关键词: 先天性肾上腺皮质增生症, CYP21A2基因, 点突变, 缺失