低深度全基因组测序拷贝数变异分析技术在性发育异常患儿诊断中的应用价值  

Application of low-depth whole genome sequencing for copy number variation analysis in children with disorders of sexdevelopment

作　　者：夏俊珂 侯雅勤[1] 代鹏[1] 赵振华[1] 陈晨[1] 孔祥东[1] Xia Junke;Hou Yaqin;Dai Peng;Zhao Zhenhua;Chen Chen;Kong Xiangdong(Prenatal and Genetic Diagnosis Center,the First Affiliated Hospital of Zhengzhou University,Zhengzhou,Henan 450002,China)

机构地区：[1]郑州大学第一附属医院遗传与产前诊断中心,郑州1450052

出　　处：《中华医学遗传学杂志》2023年第2期195-201,共7页Chinese Journal of Medical Genetics

基　　金：国家重点研发计划(2018YFC1002203)。

摘　　要：目的探讨低深度全基因组测序拷贝数变异分析(CNV-seq)技术在性发育异常(DSD)患儿诊断中的应用价值。方法纳入2019年10月至2020年10月至郑州大学第一附属医院就诊的5例身材矮小或外阴发育异常的DSD患儿。在外周血染色体核型分析、全外显子组测序(WES)、SRY基因检测的基础上,进行CNV-seq检测以明确病因。结果患儿1和2的社会性别为女性,染色体核型均为46,XY,WES结果为阴性,CNV-seq结果分别为46,XY,+Y(1.4)和46,XY,-Y(0.75)。其余3例患儿均携带可疑的Y染色体,综合分析发现其核型分别为45,X[60]/46,X,del(Y)(q11.221)[40]、45,X,16qh+[76]/46,X,del(Y)(q11.222),16qh+[24]和45,X[75]/46,XY[25]。结论联合运用CNV-seq等分子遗传学技术明确了46,XY DSD患儿的Y染色体拷贝数变异及45,X/46,XY DSD患儿可疑Y染色体的性质,为其临床诊疗提供了重要的依据。ObjectiveeTo assess the value of copy number variation sequencing(CNV-seq)for the diagnosis of children with disorders of sex development(DSD).MethodssFive children with DSD who presented at the First Affiliated Hospital of Zhengzhou University from October 2019 to October 2020 were enrolled.In addition to chromosomal karyotyping,whole exome sequencing(WES),SRY gene testing,and CNV-seq were also carried out.ResultsChild 1 and 2 had a social gender of female,whilst their karyotypes were both 46,XY.No pathogenic variant was identified by WES.The results of CNV-seq were 46,XY,+Y(1.4)and 46,XY,-Y(0.75),respectively.The remaining three children have all carried an abnormal chromosome Y.Based on the results of CNV-seq,their karyotypes were respectively verified as 45,X[60]/46,X,del(Y)(q11.221)[40],45,X,16qh+[76]/46,X,del(Y)(q11.222),16qh+[24],and45,X[75]/46,XYL25]J.Conclusion CNV-seq may be used to verify the CNVs on the Y chromosome among those with DSD and identify the abnormal chromosome in those with 45,X/46,XY.Above results have provided a basis for the clinical diagnosis and treatment of such children.

关 键 词：性发育异常 拷贝数变异 45 X/46 XY 低深度全基因组测序拷贝数变异分析 

分 类 号：R725.9[医药卫生—儿科]