一例NR5A1基因新变异所致46,XY性发育异常的遗传学分析  

Genetic analysis of 46,XY disorders of sex development in children caused by a new NR5A1 gene variant

作　　者：高龙[1] 王萍 张明英 钱莹 刘楠[2,3] 徐晓薇 王学韬 舒剑波 吕玲[1] Gao Long;Wang Ping;Zhang Mingying;Qian Ying;Liu Nan;Xu Xiaowei;Wang Xuetao;Shu Jianbo;Lyu Ling(Department of Endocrinology,Tianjin Children’s Hospital(Tianjin University Children’s Hospital),Tianjin 300134,China;Tianjin Pediatric Research Institute,Tianjin Children’s Hospital(Tianjin University Children’s Hospital),Tianjin 300134,China;Tianjin Key Laboratory of Birth Defects for Prevention and Treatment,Tianjin 300134,China)

机构地区：[1]天津市儿童医院(天津大学儿童医院)内分泌科,300134 [2]天津市儿童医院(天津大学儿童医院)儿科研究所,300134 [3]天津市儿童出生缺陷防治重点实验室,300134

出　　处：《中华医学遗传学杂志》2021年第11期1123-1126,共4页Chinese Journal of Medical Genetics

基　　金：国家自然科学基金(81771589);天津市卫生行业重点攻关项目(16KG166);天津市重大疾病防治科技重大专项(18ZXDBSY00170)。

摘　　要：目的探讨1例46,XY性发育异常(disorders of sex development,DSD)患儿的遗传学机制,并分析其基因型与表型的相关性。方法对患儿进行全外显子组测序,并对其NR5A1基因的第1~7外显子进行多重连接探针扩增检测。结果患儿表现为幼稚女童外阴,Tanner分期为1期。B超可见卵巢和子宫。患儿外周血染色体核型为46,XY,全外显子组测序发现其携带NR5A1基因第5外显子杂合缺失(chr9q33.3:127255298-127255438),为新发现的致病变异,遗传自母亲,父亲未见异常。结论46,XY DSD患儿主要表现为外生殖器男性化不足,NR5A1基因变异是其重要的遗传学病因。全外显子组测序提高了基因变异的检出率,为患儿家庭的遗传咨询提供了确切的依据。Objective To explore the genetic basis for a child with 46,XY disorders of sex development(DSD)and explore its genotype-phenotype correlation.Methods The child was subjected to whole exome sequencing(WES),and exons 1 to 7 of NR5A1 were subjected to multiplex ligation-dependent probe amplification(MLPA)analysis.Results The patient presented with rudimentary vulva of a female with Tanner stage 1.B-mode ultrasonography has detected ovary and uterus.The child was found to have a chromosome karyotype of 46,XY.WES revealed that the patient has harbored heterozygous deletion of exon 5 of the NR5A1 gene,which was a novel pathogenic variant inherited from the mother.No abnormality was found in the father.Conclusion The main symptoms of 46,XY DSD children are insufficient external genitalia masculinization,for which variants of the NR5A1 gene are an important cause.WES has improved the detection rate of genetic variants and provided a solid basis for genetic counseling of the affected families.

关 键 词：全外显子组测序 46 XY性发育异常 NR5A1基因 新变异 

分 类 号：R725.9[医药卫生—儿科]