SRY阴性46,XX性别发育异常致病原因分析  

Exploration of the pathogenesis for a SRY-negative male with 46, XX disorder of sex development

作　　者：刘爱玲 张兰雪 徐鸿雁[1] 崇宝强 刘霞霞 李琳[1] Liu Ailing;Zhang Lanxue;Xu Hongyan;Chong Baoqiang;Liu Xiaxia;Li Lin(Department of Genetics Testing,Linyi People’s Hospital,Linyi,Shandong 276003,China;Department of Laboratory Medicine,Liaocheng People’s Hospital,Liaocheng,Shandong 252000,China)

机构地区：[1]临沂市人民医院遗传检验科,276003 [2]聊城市人民医院检验科,252000

出　　处：《中华医学遗传学杂志》2020年第12期1403-1406,共4页Chinese Journal of Medical Genetics

基　　金：山东省自然科学基金联合专项(ZR2016HL07);山东省重点研发计划(2017GSF218072);山东省医药卫生科技发展计划(KT201801555)。

摘　　要：目的初步探讨SRY阴性46,XX性别发育异常(disorder of sex development,DSD)的致病原因。方法应用染色体核型分析技术、常规PCR及实时荧光定量PCR技术、全外显子测序以及全基因组测序技术对先证者及其家系成员外周血进行遗传学分析,运用NextGENe等软件进行数据分析。结果先证者及其弟弟染色体核型均为46,XX、SRY基因阴性;先证者父亲表型及染色体核型均正常,SRY基因阳性。家系成员全外显子测序未见与性别发育相关的致病性基因变异;先证者及其弟弟、父亲全基因组测序显示SOX9基因5′上游调控区域214~457 kb处存在243 kb的重复片段,而母亲和姐姐不存在该重复。结论先证者及其弟弟SOX9基因5′上游243 kb重复片段遗传自父亲,可能是导致该家系46,XX DSD的致病原因;推测该区域包含未知的SOX9基因核心调控元件,其重复可在SRY缺失下引发SOX9表达并启动睾丸分化过程。Objective To explore the pathogenesis for a SRY-negative male with 46,XX disorder of sex development(DSD).Methods Peripheral blood samples of the proband and his family members were subjected to chromosomal karyotyping,routine PCR,real-time fluorescence quantitative PCR,whole exome sequencing and whole genome sequencing.The data was analyzed with NextGENe software.Results Both the proband and his brother presented a 46,XX karyotype with negative SRY gene,while their father presented normal phenotype and karyotype with positive SRY gene.No pathogenic variant associated with sex development was detected by whole exome sequencing,while a 243 kb duplication was detected by whole genome sequencing in the 5'upstream region of the SOX9 gene in the proband,his brother and father.The same duplication was not found in his sister and mother.Conclusion The 243 kb duplication at the 5'upstream of the SOX9 gene may predispose to the 46,XX DSD in this family.It is speculated that there exist an unknown core regulatory element in the upstream of the SOX9,and its duplication may trigger expression of SOX9 and initiate testicular differentiation in the absence of SRY gene.

关 键 词：46 XX性别发育异常 SRY基因 SOX9基因 

分 类 号：R748[医药卫生—神经病学与精神病学]