雄激素不敏感综合征的遗传学研究  

Genetic features in children with androgen insensitivity syndrome

作　　者：夏俊珂 李泸平[2] 侯雅勤[1] 陈晨[1] 刘宁[1] 孔祥东[1] Xia Junke;Li Luping;Hou Yaqin;Chen Chen;Liu Ning;Kong Xiangdong(Prenatal and Genetic Diagnosis Center,Department of Gynecology&Obstetrics;Department ofPediatric Surgery,First Affiliated Hospital,Zhengzhou University,Zhengzhou 450052,China)

机构地区：[1]郑州大学第一附属医院妇产科遗传与产前诊断中心,郑州450052 [2]郑州大学第一附属医院小儿外科,郑州450052

出　　处：《中华小儿外科杂志》2024年第11期1032-1037,共6页Chinese Journal of Pediatric Surgery

基　　金：国家重点研发计划(2018YFC1002203);郑州市科技惠民计划(2021KJHM0003)。

摘　　要：目的探讨雄激素不敏感综合征(androgen insensitivity syndrome, AIS)的遗传学特点。方法回顾性分析2020年1月至2022年12月郑州大学第一附属医院收治的6例AIS患儿的临床资料, 应用染色体核型分析、全外显子测序、Sanger测序、生物信息学分析进行遗传学检测。结果 6例患儿社会性别均为女性。1例不完全性AIS患儿出生后外阴发育异常;5例完全性AIS患儿初诊年龄为1~2岁, 表现为腹股沟区肿物。仅2例患儿睾酮升高。6例患儿超声检查均未探及子宫卵巢回声, 双侧腹股沟区可探及睾丸样回声。染色体核型均为46, XY。全外显子组测序均检测到雄激素受体(androgen receptor, AR)基因半合子变异, 例4检测到2个变异。Sanger测序显示, 变异均来自母亲, 符合X连锁隐性遗传。7个变异包括错义变异5个, 插入缺失变异1个, 同义变异1个。p.Ser779Pro为新发现的变异。4例患儿行隐睾切除术, 1例行性腺活检, 病理结果均符合睾丸组织特征。结论不完全性AIS患儿常表现为男性化不足, 腹股沟肿物为完全性AIS女患儿的常见临床表型, 激素检测难以确诊。AR基因半合子变异有助于临床诊断并可以为家系遗传咨询提供依据。Objective:To explore the genetic characteristics of androgen insensitivity syndrome(AIS).Methods:Retrospective analysis was performed for 6 AIS girls from 2020 to 2022.The relevant clinical data were collected.Genetic tests were performed by karyotyping,whole exome sequencing,Sanger sequencing and bioinformatics.Results:One child with incomplete AIS presented with abnormal postnatal vulva development.Five children with complete AIS aged 1~2 years at an initial diagnosis presented with mass in bilateral inguinal region.Uterus and ovaries were invisible on ultrasonography.All gonads were testis in bilateral inguinal region.All of them had 46,XY karyotype and androgen receptor(AR)gene hemigzygous variations were detected by whole exome sequencing.Two variants were detected simultaneously in case No.4.Sanger sequencing showed that all mutations were inherited from their mothers.It was consistent with X-linked recessive inheritance.There were missense variants(n=5),indel variation(n=1)and synonymous variation(n=1).p.Ser779Pro was a novel variant.Six children were reassigned as female.Four children underwent cryptorchidectomy and 1 child had gonadal biopsy.The pathological results were consistent with testicular tissue.Conclusion:Incomplete AIS is mildly masculine.Complete AIS is characterized by groin mass in females.Hemigzygous variation of AR gene contributes to a definite diagnosis and provides rationales for genetic counseling.

关 键 词：雄激素迟钝综合征 性发育性染色体障碍 雄激素受体 同义变异 

分 类 号：R725.9[医药卫生—儿科]