目的:探讨非侵入性产前检测(NIPT)在25孕周时具有性染色体异常的胎儿的遗传特征。
方法:选择2023年1月6日因NIPT异常入院的泰州医院孕妇作为研究对象。收集相关临床资料。对胎儿进行染色体核型分析,拷贝数变异测序(CNV-seq),荧光原位杂交(FISH),和多重PCR检测。
结果:NIPT提示X染色体单倍体。胎儿染色体核型为45,X[59]/46,X,del(Y)(q11.2)[17]在30周胎龄。CNV-seq提示在Yq11.222q12处存在7.98Mb缺失和16.92Mb嵌合缺失。FISH提示胎儿有两个SRY基因和镶嵌性染色体异常,多重PCR显示其AZFb+c区完全缺失。C带核型分析在Y染色体的两端显示出深色染色的致密有丝分裂颗粒。胎儿最终被确定为45,X/46,X,idic(Y)(q11.2)镶嵌。在选举堕胎之后,胎儿组织的测试证实存在45,X/46,XY镶嵌,胎盘组织的CNV-seq结果与NIPT一致。夫妇的CNV-seq分析显示无明显异常。
结论:结合NIPT,核型分析,CNV-seq,FISH和多重PCR检测,胎儿被诊断为45,X/46,X,idic(Y)(q11.2)镶嵌,AZFb+c区缺失。上述发现使胎儿能够进行产前诊断。
OBJECTIVE: To explore the genetic characteristics of a
fetus with sex chromosome abnormality indicated by non-invasive prenatal testing (NIPT) at 25+ gestational weeks.
METHODS: A pregnant woman who was admitted to the Taizhou Hospital for abnormal NIPT result on January 6, 2023 was selected as the study subject. Relevant clinical data was collected. The
fetus was subjected to chromosomal karyotyping analysis, copy number variation sequencing (CNV-seq), fluorescence in situ hybridization (FISH), and multiplex PCR assays.
RESULTS: NIPT had suggested monosomy of X chromosome. The
fetus was found to have a chromosomal karyotype of 45,X[59]/46,X,del(Y)(q11.2)[17] at 30+ weeks of gestational age. CNV-seq suggested the presence a 7.98 Mb deletion at Yq11.222q12 and a mosaicism 16.92 Mb deletion. FISH suggested that the fetus harbored two SRY genes and a mosaicism sex chromosomal abnormality, and multiplex PCR revealed that its AZF b+c region was completely deleted. C-banded karyotyping showed darkly stained dense mitotic granules at both ends of the Y chromosome. The
fetus was ultimately determined as a 45,X/46,X,idic(Y)(q11.2) mosaicism. Following elected abortion, testing of the fetal tissue confirmed the presence of 45,X/46,XY mosaicism, and CNV-seq result of the placental tissue was compatible with that of NIPT. CNV-seq analysis of the couple revealed no obvious abnormality.
CONCLUSIONS: With combined NIPT, karyotyping, CNV-seq, FISH and multiplex PCR assays, the fetus was diagnosed as a 45,X/46,X,idic(Y)(q11.2) mosaicism with deletion of the AZF b+c region. Above finding has enabled prenatal diagnosis for the
fetus.