雄激素不敏感综合征临床与遗传学分析

Clinical and genetic analysis of androgen insensitivity syndrome

目的:分析雄激素不敏感综合征(androgen insensitivity syndrome,AIS)的临床特征与遗传学特点。方法:收集2015年至2020年重庆医科大学附属儿童医院就诊的10例AIS患者临床资料,提取患儿及父母外周血DNA,对患儿DNA样本进行内分泌疾病相关基因高通量测序,并进行家系DNA样本Sanger测序验证。结果:10例患者均检测到雄激素受体(androgen receptor,AR)基因变异,其中5个变异以前未报道过,分别是c.401dupA(p.P135Afs23)、1 350 bp缺失突变、c.2505C>G(p.Y835X)、c.1747T>C(p.F583L)和c.610G>T(p.E204X),其中c.610G>T(p.E204X)为嵌合体突变。结论:本研究中5例未报道变异均可能致病,提示基因检测有助于AIS的确诊,有利于AIS患者的临床决策和遗传咨询。

Objective:To analyze the clinical and genetic characteristics of androgen insensitivity syndrome(AIS). Methods:Clinical data of 10 AIS patients who were treated in the Children’s Hospital of Chongqing Medical University from 2015 to 2020 were collected in the study. The DNA was extracted from the peripheral blood of the children and their parents. The endocrine disease-related genes were sequenced,and family DNA samples were verified by Sanger sequencing. Results:Androgen receptor(AR) gene mutations were identified in all patients,of which five mutations had not been described previously,namely c.401dupA(p.P135Afs23),1 350 bp deletion mutation,c.2505C>G(p.Y835X),c.1747T>C(p.F583L) and c.610G>T(p.E204X). Among them,c.610G>T(p.E204X) was a chimera mutation. Conclusion:All five undescribed mutations in this study may be pathogenic,suggesting that gene testing is helpful to the diagnosis of AIS,and is beneficial to clinical decision-making and genetic counseling of AIS patients.