Wu Dingwen,Wu Dehua,Zheng Jing,et al.Correlations between phenotype and monogenic mutation of 46,XY sexual development disorder[J].Journal of Clinical Pediatric Surgery,,18():191-195.[doi:10.3969/j.issn.1671-6353.2019.03.006]
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Correlations between phenotype and monogenic mutation of 46,XY sexual development disorder

Journal of Clinical Pediatric Surgery[ISSN:1671-6353/CN:43-1380/R] volume: 第18卷 Number: 2019 03 Page: 191-195 Column: 专题·儿童性别发育异常 Date of publication: 2019-03-25
Author(s):
Wu Dingwen1;  Wu Dehua2;  Zheng Jing1;  Tian Hongjuan2;  Zhang Ting1;  Tao Chang2;  Shen Yaping1;  Chen Guangjie2;  Tang Daxing2
1. Department of Genetics & Metabolism, Affiliated Children’s Hospital, Zhejiang University School of Medicine;Key Laboratory of Diagnosing & Treating Neonatal Diseases of Zhejiang Province, Hangzhou 310052, China;
2. Department of Urology, Affiliated Children’s Hospital, Zhejiang University School of Medicine, Hangzhou 310052, China
Keywords:
Gonadal Dysgenesis; 46; XY/Embryo; Genes/Genetics
CLC:
R726.9;R691.1;R393
DOI:
10.3969/j.issn.1671-6353.2019.03.006
Abstract:
Objective To explore the correlations between various phenotypes and monogenic mutations of 46,XY sexual development disorder (DSD) and provide valuable rationales for clinical application.Methods Genomic DNA was isolated from peripheral blood of 137 patients of 46,XY DSD.The exons of 2742 pathogenic genes were acquired by liquid phase capture technology.Variants on coding region and 10 bp around exon region of these genes were obtained by high throughput sequencing and bioinformatic analysis.And classification was performed according to the ACMG criteria.Furthermore,these patients were divided into 6 groups according to their clinical phenotypes,including cryptorchidism or small testicle,hypospadias,small penis or occult penis,multiple DSD phenotypes,hermaphroditism and DSD syndrome.Then the rate of positive findings and diagnostic yield of different groups and associated gene mutations were analyzed.Results Positive/likely positive mutations with clinical value were identified in 62/137 patients involving 23 genes with an overall positive detection rate of 45.26% (SRD5A2,AR,NR5A1,AMH,FGFR1,PROKR2,DMRT1,MAmLD1,WT1,ZEB2,AKR1C2,CHD7,CYP17A1,DMRT2,FGD1,FRAS1,GATA4,MAP3K1,POR,SAMD9,TACR3,VANGL1,WNT5A).Furthermore,the diagnostic yield of characterized disease genes among patients with 46,XY DSD was 26.28% (36/137).Those with multiple DSD phenotypes,hermaphroditism and DSD syndrome had a higher rate of positive findings with the frequencies of 57.14%,86.36% & 66.67% as well as diagnostic yield with the frequencies of 28.57%,63.64% & 50.00% respectively than those with cryptorchidism or small testicle,hypospadias,small penis or occult penis.Conclusion Monogenic mutation is an important genetic cause of 46,XY DSD.The rate of positive findings and diagnostic yield are positively correlated with the severity of 46,XY DSD phenotype.Targeted capturing plus high-throughput sequencing may be used as the preferred method for genetic testing of hermaphroditism,syndromic DSD and multiple DSD phenotypes.

References:

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Memo

收稿日期:2018-11-07。
基金项目:国家重点研发计划（编号：2018YFC1002700）；浙江省分析测试科技计划（编号：2018C3706）；浙江省医药卫生科技计划（编号：2015KYA118）
通讯作者:唐达星,Email:tangdx0206@zju.edu.cn

Last Update: 1900-01-01