先天性肾上腺皮质增生症患者家系基因分析

目的对1例存在外阴和乳晕色素沉着的新生儿期确诊的先天性肾上腺皮质增生症患儿家系相关基因特点进行分析,明确其基因突变的类型及来源,为诊疗及遗传咨询提供依据。方法(1)采集患儿及父母外周血,应用过柱法提取DNA,应用测序技术,对先天性肾上腺皮质增生症(CAH)相关基因CYP21A2、CYP11B1、HSD3B2、CYP17A1、STAR的外显子编码区进行直接测序,并与参考序列进行比较,从而发现可能存在的基因突变。(2)应用多重连接酶探针依赖扩增(MLPA)技术检测待检样本的CYP21A2基因各外显子,用正常人的DNA作为参照,检测CYP21A2基因是否发生缺失/重复突变。结果患儿:检测到致病性的基因变异:(1)CYP21A2 c.-126C>T,杂合;(2)CYP21A2 c.-113G>A,杂合;(3)CYP21A2 c.293-13C>G,杂合;(4)CYP21A2 Exon1、3 del,杂合;未检测到CYP11B1、HSD3B2、CYP17A1、STAR基因外显子编码区的致病性变异;应用MLPA技术检测到CYP21A2基因杂合的大片段缺失突变;患儿父亲:检测到致病性的基因变异:(1)CYP21A2 c.-126C>T,杂合;(2)CYP21A2 c.-113G>A,杂合;(3)CYP21A2:c.293-13C>G,杂合;患儿母亲:检测到致病性的基因变异:CYP21A2 Exon1、3 del,杂合。结论CYP21A2基因发生致病性变异可引起先天性肾上腺皮质增生症。携带致病性变异的父母生育前建议至有资质的机构进行遗传咨询。对外阴和乳晕色素沉着及性腺发育异常的患儿建议行基因检测以期做到早期诊断,早期治疗。

Gene Sequencing of the Neonate and Her Family Members With 21-Hydroxylase Deficiency

Objective To analyze the gene mutation characteristics of 21-hydroxylase deficiency in one family,and to provide the basis for clinical diagnosis and guidance for genetic consultancy.Methods Point mutations,deletions and conversion mutations for gene CYP21A2 coding 21-hydroxylase were detected through using gene sequencing and muhiplex ligation-dependent probe amplification(MLPA)among the neonate and her family members.Results The neonate:those mutated sites were captured:(1)CYP21A2 c.-126C>T,heterozygote;(2)CYP21A2 c.-113G>A,heterozygote;(3)CYP21A2 c.293-13C>G,heterozygote;(4)CYP21A2 Exon1,3 del,heterozygote.Her farther:(1)CYP21A2 c.-126C>T,heterozygote;(2)CYP21A2 c.-113G>A,heterozygote;(3)CYP21A2 c.293-13C>G,heterozygote.Her mother:CYP21A2 Exon1,3 del heterozygote.Conclusion Gene sequencing is helpful to early diagnosis of Congenital adrenal hyperplasia,differential diagnosis and optimized treatment,which will improve prognosis and provide guidance for genetic consultancy.