Application of low-depth whole genome sequencing for copy number variation analysis in children with disorders of sex development
夏俊珂 1侯雅勤 1代鹏 1赵振华 1陈晨 1孔祥东 1鞠翠钰 李岭
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作者信息
1. 郑州大学第一附属医院遗传与产前诊断中心，郑州 450052
折叠
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。 Objective To assess the value of copy number variation sequencing (CNV-seq) for the diagnosis of children with disorders of sex development (DSD). Methods Five 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. Results Child 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], and 45, X[75]/46, XY[25]. 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.
Abstract
Objective To assess the value of copy number variation sequencing (CNV-seq) for the diagnosis of children with disorders of sex development (DSD). Methods Five 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. Results Child 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], and 45, X[75]/46, XY[25]. 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
Key words
Disorders of sex development/Copy number variation/45, X/46, XY/copy number variation sequencing
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