Zhang Wanyu,Ye Weijing,Shi Jinxiu,et al.Genotype and clinical phenotype analysis of 110 46,XY disorders of sex development in children[J].Journal of Clinical Pediatric Surgery,2019,18(12):1036-1042.[doi:10.3969/j.issn.1671-6353.2019.12.010]
46，XY性发育异常患儿基因型与临床表型分析
- Title:
- Genotype and clinical phenotype analysis of 110 46,XY disorders of sex development in children
- Keywords:
- Sexual Development; Genotype; Hypospadias
- 分类号:
- R726.9;R691.1;R394
- 摘要:
- 目的 利用靶向二代测序技术对110例46，XY性发育异常（DSD）患儿进行基因检测，初步探讨该类疾病患儿的基因型和临床表型。方法 收集2017-2018年就诊于上海交通大学医学院附属瑞金医院和仁济医院110例诊断为46，XY DSD患儿的临床资料；对患儿进行靶向二代测序，筛选出致病基因；分析患儿基因型和临床表型。结果 共发现16例患儿存在基因变异，涉及6种基因的13个变异位点。8例患儿存在5种SRD5A2基因变异（p.Q6X、p.L20P、p.G203S、p.R227Q、p.P251S），其中p.P251S为新发变异位点；4例患儿存在4种AR基因变异（p.Q58L、p.A597T、p.R608Q和p.A871V）；2例患儿存在PROKR2基因杂合变异（p.W178S），其中1例患儿合并SRD5A2基因变异；1例合并法洛四联症的患儿存在ZFPM2基因杂合变异（p.M703L）；1例患儿存在BMP4基因杂合变异（p.H251Y）；1例患儿存在CHD7基因杂合变异（p.T730I）。16例基因变异患儿临床表型多样，其中9例为尿道下裂合并小阴茎，6例为尿道下裂、小阴茎和隐睾，1例为尿道下裂合并隐睾。结论 尿道下裂合并小阴茎和（或）隐睾可能提示患儿存在基因变异。尿道下裂基因变异率为14.5%（16/110），其中SRD5A2和AR为最常见变异基因。尽管ZFPM2、PROKR2、BMP4和CHD7作为候选基因检出率不高，但亦不可忽略。
- Abstract:
- Objective To detect the pathogenic genes of 110 patients with 46,XY disorders of sex development (DSD) by a targeted panel of next-generation sequencing (NGS) and examine the genotype and clinical phenotype of hypospadias patients.Methods Clinical data of 110 46,XY DSD patients at Affiliated Ruijin and Renji Hospitals from 2017 to 2018 were reviewed and analyzed.We performed sequencing analysis for 110 patients with hypospadias of unknown etiology for screening for pathogenic genes.Results A total of 16 children had genetic variations involving 13 mutation sites of 6 genes.Five different SRD5A2 mutations (p.Q6X,p.L20P,p.G203S,p.R227Q & p.P251S) were detected in 8 cases and one novel mutation (p.P251S) was identified.Four different AR pathogenic mutations(p.Q58L,p.A871V,p.R608Q & p.A597T)were detected in four cases.One PROKR2 heterozygous mutation (p.W178S) was found in 2 cases,including 1 case of SRD5A2 gene mutation.One ZFPM2 heterozygous mutation (p.M703L) was detected in one child with Tetralogy of Fallot.There were BMP4 gene heterozygous variation (p.H251Y) (n=1) and CHD7 heterozygous variation (p.T730I) (n=1).And 16 patients with gene mutation presented a variety of clinical phenotypes,including hypospadias with small penis (n=9),hypospadias,small penis & cryptorchidism (n=6) and hypospadias with cryptorchidism (n=1).Conclusion Hypospadias with small penis and/or cryptorchidism may indicate genetic mutations.The mutation rate of hypospadias gene is 14.5% (16/110) and SRD5A2 and AR are two most common mutated genes.Despite low detection rates of ZFPM2,PROKR2,BMP4 and CDD7,they should not be ignored.
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备注/Memo
收稿日期:2019-02-20。
基金项目:浦东新区科技发展基金项目（编号：Pkj-z04）
通讯作者:董治亚,Email:dzy831@126.com