CYP11B2/CYP11B1融合基因致11β羟化酶缺乏症1例的遗传学分析  

Genetic analysis of a case with 11βhydroxylase deficiency caused by CYP11B2/CYP11B1 chimeric gene

作　　者：林一凡 杨海花[1] 袁淑娴 李东晓 卫海燕[1] 马晓翠 Lin Yifan;Yang Haihua;Yuan Shuxian;Li Dongxiao;Wei Haiyan;Ma Xiaocui(Department of Endocrinology,Genetics and Metabolism,Children′s Hospital Affiliated to Zhengzhou University,Henan Children′s Hospital,Zhengzhou,Henan 450018,China;Laboratory of Genetic Metabolic Diseases,Children′s Hospital Affiliated to Zhengzhou University,Henan Children′s Hospital,Zhengzhou,Henan 450018,China)

机构地区：[1]郑州大学附属儿童医院,河南省儿童医院内分泌遗传代谢科,郑州450018 [2]郑州大学附属儿童医院,河南省儿童遗传代谢性疾病重点实验室,郑州450018

出　　处：《中华医学遗传学杂志》2023年第4期462-467,共6页Chinese Journal of Medical Genetics

基　　金：河南省科技攻关计划(212102310438)。

摘　　要：目的探讨1例CYP11B2/CYP11B1融合基因所致11β羟化酶缺乏症(11β-OHD)患儿的遗传学特征,并为其父母提供产前遗传咨询。方法选取1例2020年8月24日就诊于河南省儿童医院内分泌科的患儿为研究对象。收集患儿临床资料,采集患儿及其父母的外周血样,对患儿进行全外显子组测序(WES),对候选变异进行Sanger测序家系验证。用RT-PCR及Long-PCR确定患儿的融合基因。结果患儿为5岁男性,第二性征发育提前,生长加速,诊断为21羟化酶缺乏症(21-OHD)。WES检测提示患儿CYP11B1基因存在杂合错义变异c.1385T>C(p.L462P),同时染色体8q24.3区存在37.02 kb的杂合缺失。根据美国医学遗传学与基因组学学会(ACMG)相关指南,将c.1385T>C(p.L462P)评级为可能致病变异(PM2_Supporting+PP3_Moderate+PM3+PP4)。RT-PCR及Long-PCR联合检测结果提示为CYP11B1和CYP11B2基因重组,形成CYP11B2 exon 1~7/CYP11B1 exon 7~9融合基因。患儿被确诊为11β-OHD,经氢化可的松及曲普瑞林治疗有效。患儿父母经遗传咨询后娩1个健康后代。结论因CYP11B2/CYP11B1融合基因所致的11β-OHD易被误诊为21-OHD,需采用多种基因检测手段联合进行诊断。Objective To analyze a child with 11βhydroxylase deficiency(11β-OHD)due to CYP11B2/CYP11B1 chimeric gene.Methods Clinical data of the child who was admitted to Henan Children′s Hospital on August 24,2020 were retrospectively analyzed.Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing(WES).Candidate variant was verified by Sanger sequencing.RT-PCR and Long-PCR were carried out to verify the presence of chimeric gene.Results The patient,a 5-year-old male,had featured premature development of secondary sex characteristics and accelerated growth,and was diagnosed with 21 hydroxylase deficiency(21-OHD).WES revealed that he has harbored a heterozygous c.1385T>C(p.L462P)variant of the CYP11B1 gene,in addition to a 37.02 kb deletion on 8q24.3.Based on the guidelines from the American College of Medical Genetics and Genomics(ACMG),the c.1385T>C(p.L462P)was rated as a likely pathogenic variant(PM2_Supporting+PP3_Moderate+PM3+PP4).The results of RT-PCR and Long-PCR suggested that CYP11B1 and CYP11B2 genes have recombined to form a CYP11B2 exon 1~7/CYP11B1 exon 7~9 chimeric gene.The patient was diagnosed as 11β-OHD and effectively treated with hydrocortisone and triptorelin.A healthy fetus was delivered following genetic counseling and prenatal diagnosis.Conclusion 11β-OHD may be misdiagnosed as 21-OHD due to the potential CYP11B2/CYP11B1 chimeric gene,which will require multiple methods for the detection.

关 键 词：类固醇11-β-羟化酶 11β羟化酶缺乏症 CYP11B1基因 CYP11B2/CYP11B1融合基因 儿童 

分 类 号：R725.8[医药卫生—儿科]