21-羟化酶缺乏症CYP21A2基因突变及表型分析  

Analysis of CYP21A2 gene mutation and phenotype in patients with 21-hydroxylase deficiency

作　　者：舒剑波[1] 张新杰 徐晓薇 邹倩倩 王朝 孟英韬[1] 蔡春泉[2] 林书祥[1] 黄乐[3] 吕玲[3] Shu Jianbo;Zhang Xinjie;Xu Xiaowei;Zou Qianqian;Wang Chao;Meng Yingtao;Cai Chunquan;Lin Shuxiang;Huang Le;Lyu Ling(Tianjin Pediatric Research Institute,Tianjin Children's Hospital,Tianjin 300134,China;Department of Neurosurgery ,Tianjin Children's Hospital,Tianjin 300134,China;Department of Endocrinology,Tianjin Children's Hospital,Tianjin 300134,China)

机构地区：[1]天津市儿童医院天津市儿科研究所,300134 [2]天津市儿童医院神经外科,300134 [3]天津市儿童医院内分泌科,300134

出　　处：《中华内分泌代谢杂志》2019年第1期21-25,共5页Chinese Journal of Endocrinology and Metabolism

基　　金：天津市自然科学基金青年项目(16JCQNJC11900);国家自然科学基金项目(81771589);天津市重大疾病防治科技重大专项(18ZXDBSY00170).

摘　　要：目的探讨天津及周边地区21-羟化酶缺乏症患者CYP21A2基因突变谱,分析基因型与表型的相关性。方法收集先证者外周血,提取基因组DNA,联合应用位点特异性PCR、PCR扩增产物直接测序以及多重连接依赖探针扩增技术对致病基因CYP21A2进行检测并分析基因型与临床表型的关系。结果(1)在35例21-羟化酶缺乏症患儿中,25例为失盐型,10例为单纯男性化型。(2)在35例先证者70个等位基因中共检测出69个突变等位基因,除1例只检出1个突变等位基因外,其他患者均检测出2个突变等位基因,突变检出率为98.6%。(3)共检出6种突变,其中c.293-13C/A>G(12G)最为常见,占57.1%(40/70),其次为大片段缺失或基因转换,占18.6%(13/70),第三是p.I173N,占14.3%(10/70)。另外还检出了一个国内外均未报道过的新突变c.949C>T(p.R317X),为致病性变异。(4)对35例患儿进行基因型与表型相关性分析,结果显示31例患儿依据基因型预测的表型与实际失盐表型一致,3例患儿与实际临床表型不一致。结论天津及周边地区21-羟化酶缺乏症患者CYP21A2基因突变特点与国内其他地区报道略有不同,其中c.949C>T尚未见报道,这丰富了21-羟化酶缺乏症致病基因CYP21A2的突变谱,为遗传咨询及产前诊断奠定了基础。Objective To investigate the spectrum of CYP21A2 gene mutation and the correlation between genotype and phenotype in patients with 21-hydroxylase deficiency in Tianjin and surrounding areas.Methods Genomic DNA was extracted from the peripheral blood samples of the proband.Locus-specific PCR,direct sequencing of PCR amplification products,and multiplex ligation-dependent probe amplification were applied to detect pathogenic gene CYP21A2 and the relationship between genotypes and phenotypes was analyzed.Results (1 )Of 35 patients with 21-hydroxylase deficiency,25 were classified as salt-wasting phenotype and 10 were simple virilizing phenotype.(2)69 mutant alleles were detected in a total of 70 alleles in 35 patients.Only one mutant allele was detected in one patient.Two mutant alleles were detected in all other patients,with the mutation detection rate 98.6%.(3)A total of 6 types of mutations were detected,of which c.293-13C/A>G (I2G)was the most common, accounting for 57.1%(40/70),followed by 18.6%(13/70)for large gene deletion or conversion,and 14.3%(10/ 70)for p.I173N.In addition,a novel mutation,c.949C>T (p.R317X),which has not been reported previously,was detected as a pathogenic mutation.(4)Correlation analysis of genotype and phenotype in 35 children showed that the phenotype predicted by genotype was consistent with the actual salt-wasting phenotype in 31 children,and those in three children were inconsistent with the actual clinical phenotype.Conclusion The mutation characteristics of CYP21A2 gene in patients with 21-hydroxylase deficiency in Tianjin and surrounding areas are slightly different from those reported in other regions in China.A mutation c.949C>T has not been reported,which enriches the mutation spectrum of CYP21A2 gene and provide the foundation for genetic counseling and prenatal diagnosis.

关 键 词：21-羟化酶缺乏症 CYP21A2基因 突变 

分 类 号：R725.8[医药卫生—儿科]