山西省21-羟化酶缺乏症基因型与临床表型相关性分析

Correlation between genotype and clinical phenotype of 21-hydroxylase deficiency in Shanxi province

目的研究山西省21-羟化酶缺乏症患儿的基因突变,探讨基因型和临床表型的相关性。方法回顾性分析2014年1月至2016年10月山西省儿童医院收治的15例21-羟化酶缺乏症患儿的临床资料,采用Sanger测序法进行CYP21A2基因突变分析。CYP21A2基因检测结果与其临床表型进行比较,分析基因型与临床表型的相关性。结果 (1)本组15例患儿均为经典型患者,其中失盐型(SW)8例,单纯男性化型(SV)7例。(2)15例患儿共检测出7种突变,包括IVS2-13A/C>G、I172N、R356W、E3Δ8bp、c.1064G>A、c.141C>A、c.121C>T。最常见的突变为IVS2-13A/C>G(40%),其余常见突变依次为R356W(17%)、I172N(17%)及E3Δ8bp(7%)。SW最常见的突变为IVS2-13A/C>G和R356W,其等位基因频率分别达50%和19%。SV患者最常见的突变为I172N,其等位基因频率为36%。(3)SW、SV中基因型与临床表型的阳性预测值分别为88%、100%。结论 IVS2-13A/C>G、R356W、I172N为21-羟化酶缺乏症患儿常见突变,山西省热点突变为IVS2-13A/C>G。经典型患儿基因型与临床表型具有明显相关性。

Objective To determine the gene mutation in children with 21-hydroxylase deficiency（21-OHD） in Shanxi province, and to investigate the correlation between the genotype and clinical phenotype. Methods The clinical data of 15 children with 21-OHD, who were hospitalized in the Shanxi Provincial Children′ s Hospital between October 2014 and October 2016, were analyzed retrospectively. The Sanger sequencing was used for the mutation analysis of CYP21A2 gene. The findings of CYP21A2 gene test were compared with its clinical phenotype, and the correlation between the genotype and clinical phenotype was compared. Results（1） The 15 children in this group were all typical patients, including 8 cases of salt wasting（SW） type and 7 cases of simple virilizing（SV） type.（2）A total of 7 mutations were detected in the 15 children, including IVS2-13A/C〉G, I172 N, R356 W, E3Δ8bp, c.1064G〉A,c.141C〉A, and c.121C〉T. The most common mutation was IVS2-13A/CG（40%）, and the other common mutations were R356W（17%）, I172N（17%） and E3Δ8bp（7%）. The most common mutations of SW were IVS2-13A/CG and R356 W, and the allele frequencies were 50% and 19%, respectively. The most common mutation in SV patients was I172 N, and its allele frequency was 36%.（3）The positive predictive values of the genotype and clinical phenotype in SW and SV were 88% and 100%, respectively. Conclusion The IVS2-13A/C-G, R356 W and I172 N are common mutations in children with 21-OHD, and the hot spot mutation in Shanxi province is IVS2-13A/CG. There is a significant correlation between the genotype and clinical phenotype in patients with classical type.