Y染色体长臂嵌合缺失胎儿1例的遗传学分析  

Genetic analysis of a fetus with mosaicism Y chromosome aberration

作　　者：孟凡荣[1,2] 琚端 王秀艳[1,2] 史云芳 杨萌 李晓洲[1,2] Meng Fanrong;Ju Duan;Wang Xiuyan;Shi Yunfang;Yang Meng;Li Xiaozhou(Tianjin Key Laboratory for Female Reproductive Health and Birth Health,Department of Gynecology and Obstetrics,Tianjin Medical University General Hospital,Tianjin 300052,China)

机构地区：[1]天津医科大学总医院妇产科 [2]天津市女性生殖健康与优生重点实验室,天津300052

出　　处：《中华医学遗传学杂志》2023年第11期1414-1419,共6页Chinese Journal of Medical Genetics

基　　金：国家自然科学基金(81901502);天津医科大学总医院孵育基金(ZYYFY2019022);天津市医学重点学科(专科)建设项目资助(TJYXZDXK-031A)。

摘　　要：目的对1例Y染色体长臂嵌合缺失胎儿提供遗传咨询和产前诊断。方法选取2021年7月在天津医科大学总医院就诊的1例无创产前检测(NIPT)提示性染色体高风险的胎儿为研究对象。通过染色体G显带核型分析、荧光原位杂交技术(FISH)、拷贝数变异测序(CNV-seq)、荧光定量PCR(QF-PCR)及超声检查等多种方法联合应用对胎儿进行产前诊断。结果胎儿(胎龄23周)羊水细胞染色体核型为45,X,然而FISH检测可见Y染色体信号。脐带血穿刺复核,核型结果为嵌合型染色体异常46,X,+mar[33]/45,X[17];FISH检测提示69%的细胞可见Y染色体信号;CNV-seq检测结果为seq[19]del(Y)(q11.1q12)(mos)chrY:g.13200001_28820000del(嵌合比例64%),即包括无精症因子(azoospermia factor,AZF)区域的Y染色体长臂嵌合缺失;应用QF-PCR技术对AZF区域缺失进行验证,与CNV-seq结果一致。最终胎儿核型描述为mos 46,X,del(Y)(q11.1)[33]/45,X[17]。超声检查胎儿未见异常。孕妇终止妊娠,引产儿外观未见异常,外生殖器表现为正常男性。结论多种检测技术联合应用有利于准确快速的产前诊断。嵌合性性染色体异常胎儿的出生后表型难以准确评估,应尽可能探索基因型-表型联系,为遗传咨询提供更全面准确的指导。Objective To carry out prenatal diagnosis for a fetus with mosaicism Yq deletion.Methods A fetus with high risk of sex chromosomes indicated by non-invasive prenatal testing(NIPT)at Tianjin Medical University General Hospital in July 2021 was selected as the study subject.Prenatal diagnosis of the fetus was performed with combined G-banded chromosomal karyotyping,fluorescence in situ hybridization(FISH),copy number variation sequencing(CNV-seq),real-time fluorescence PCR(QF-PCR),and ultrasound examination.Results Analysis of the amniocytes at 23 gestational weeks had yielded a 45,X karyotype.However,FISH had shown signals of Y chromosome.Re-examination by cordocentesis had shown a mosaicism of 46,X,+mar[33]/45,X[17].FISH showed that 69%of the cells had contained Y chromosome signals.The result of CNV-seq was seq[19]del(Y)(q11.1q12)(mos)chrY:g.13200001_28820000del(mosaicism rate=64%),which suggested mosaicism for a Yq deletion,which encompassed the azoospermia factor(AZF)region.Deletion of the AZF region was verified by QF-PCR.The fetal karyotype was ultimately determined as mos46,X,del(Y)(q11.1)[33]/45,X[17].Although ultrasound examination had shown no abnormality in the fetus,the couple had opted to terminate the pregnancy,and the induced fetus had a normal male appearance.Conclusion The combined use of multiple techniques is beneficial for accurate and rapid prenatal diagnosis.For fetuses with mosaicism chromosomal abnormalities,it may be difficult to accurately predict the postnatal phenotype.It is therefore necessary to further explore their genotype-phenotype correlation in order to provide better guidance upon genetic counseling.

关 键 词：染色体核型分析 产前诊断 荧光原位杂交 拷贝数变异测序 无精症因子 

分 类 号：R714.5[医药卫生—妇产科学]