18例21-羟化酶缺陷症患者临床表型及CYP21A2基因变异分析  

Analysis of clinical phenotypes and CYP21A2 gene variants in 18 patients with 21-hydroxylase deficiency

作　　者：郑瑞芝[1] 张俐[1] 袁倩[1] 曼华[1] 杨俊朋[1] 汪艳芳[1] 虎子颖[1] 张会峰[1] Zheng Ruizhi;Zhang Li;Yuan Qian;Man Hua;Yang Junpeng;Wang Yanfang;Hu Ziying;Zhang Huifeng(Department of Endocrinology,Henan Provincial People's Hospital,Zhengzhou,Henan 450003,China)

机构地区：[1]河南省人民医院内分泌科,郑州450003

出　　处：《中华医学遗传学杂志》2019年第2期120-123,共4页Chinese Journal of Medical Genetics

基　　金：河南省科技厅基础与前沿技术研究项目(142300410071);河南省卫生厅医学学术技术带头人出国培训计划项目(201201086);河南省卫生厅科技攻关计划项目(201303123).

摘　　要：目的 探讨21-羟化酶缺陷症(21- hydroxylase deficiency, 21-OHD)患者的基因型与临床表型的关系。 方法 应用PCR-直接测序法对18例21-OHD患者和20名正常对照CYP21A2基因的10个外显子及其侧翼序列进行测序。 结果 在18例患者中,17例检测出CYP21A2基因变异,其中纯合变异8例(44.4%,8/18),复合杂合变异6例(33.3%,6/18),单一杂合变异3例;纯合变异分别为c.518 T>A(p.Ile173Asn)(62.5%,5/8)、c.92 C>T (p.Pro31Leu)(25.0%,2/8)、IVS2 -13 A>G(12.5%,1/8),复合杂合变异以IVS2 -13 A>G和c.518 T>A(p.Ile173Asn)复合杂合变异最为常见(50.0%)。致病等位基因变异占94.4% (34/36),最常见的变异位点为c.518 T>A(p.Ile173Asn) (41.7%)、IVS2 -13 A>G (19.4%)和c.92 C>T(p.Pro31Leu) (13.9%)。20名正常对照均未检测到这些变异。 结论 绝大多数21-OHD患者均存在CYP21A2基因变异,以纯合变异或复合杂合变异为主,c.518 T>A(p.Ile173Asn)等位基因变异最为常见。基因型和临床表型有较高的一致性。Objective To explore the genotype-phenotype correlation among 18 patients with 21-hydroxylase deficiency (21-OHD).Methods PCR-Sanger sequencing was used to analyze the 10 exons and flanking regions of the CYP21A2 gene among the 18 patients and 20 healthy controls.Results Seventeen patients had variants of the CYP21A2 gene. Eight patients (44.4%, 8/18) carried homozygous variants including p. Ile 173Asn (62.5%, 5/8), p. Pro31Leu (25.0%, 2/8), and IVS2-13A/C>G (12.5%, 1/8), respectively. Six patients (33.3%, 6/18) carried compound heterozygous variant, among which IVS2-13 A>G+ p.Ile 173Asn were most common (50.0%). 94.4% (34/36) of the variant were pathogenic, with the most common variants being p. Ile173Asn (41.7%), IVS2-13A/C>G (19.4%), and p. Ile173Asn (7.5%). No variants was identified among the 20 healthy controls.Conclusion The majority of 21-OHD patients carried CYP21A2 gene variants in homozygous or compound heterozygous forms, among which the p. Ile173Asn was the most common one. There is a strong correlation between the genotypes and clinical phenotypes.

关 键 词：先天性皮质醇增多症 21-羟化酶缺陷症 CYP21A2基因 

分 类 号：R586[医药卫生—内分泌]