884例性染色体异常胎儿产前诊断结果分析

Prenatal diagnosis result analysis of 884 fetuses with sex chromosomal abnormalities

目的 对884例无创产前筛查(NIPS)提示性染色体异常的羊水样本进行核型分析、荧光原位杂交技术(FISH)和拷贝数变异测序(CNV-seq)检测,探讨不同方法在产前诊断中的价值。方法 选取2015年1月—2022年12月天津市中心妇产科医院孕早期NIPS提示胎儿为性染色体异常的孕妇884例,于孕中期采集羊水样本,进行羊水细胞核型分析和FISH检测,对结果不一致或培养失败的样本进一步行CNV-seq检测。结果 884例孕妇中,有341例(38.6%)检出异常核型,11例(1.2%)羊水细胞培养失败。NIPS性染色体阳性预测值为39.2%(341/873)。341例核型分析异常样本中,最常见的核型异常类型是47,XXY(108例),其次为47,XXX(80例)、47,XYY(68例)、45,X(18例),共检出51例嵌合体。884例孕妇中,有862例FISH检测结果与核型分析或CNV-seq结果一致,FISH的阳性预测值为97.5%;24例与核型分析结果不一致,进一步行CNV-seq检测,有22例CNV-seq结果与核型分析结果一致,并能相互补充分析;2例不一致样本中,1例核型分析结果为46,~+mar,FISH和CNV-seq结果均为45,X;1例核型分析结果为嵌合Y染色体异染色质区缺失,FISH和CNV-seq结果均为嵌合体,结构未见异常。结论 NIPS提示性染色体异常时,建议首选FISH和核型分析联合检测,可快速、准确地诊断染色体异常。对于疑似染色体特殊结构异常,建议进行FISH、核型分析和CNV-seq联合检测,可明确遗传学病因。

Objective To perform karyotype analysis,fluorescence in situ hybridization(FISH)and copy number variation sequencing(CNV-seq)on 884 amniotic fluid samples with non-invasive prenatal screening(NIPS)sex chromosomal abnormalities,and to investigate the roles of different methods in prenatal diagnosis.Methods A total of 884 patients who received NIPS in thefirst trimester of pregnancy and indicated that the fetus was with sex chromosomal abnormality were enrolled from Tianjin Central Hospital of Gynecology and Obstetrics from January 2015 to December 2022.Amnioticfluid samples were collected in the second trimester of pregnancy,and karyotype analysis and FISH were performed.CNV-seq was further performed on the samples with inconsistent results or culture failure.Results In the 884 cases,341 cases(38.6%)of abnormal karyotype were determined,amniotic fluid cell culture failed in 11 cases(1.2%),and the positive predictive value was 39.2%(341/873).Among the 341 fetuses with abnormal karyotype analysis,the most common abnormal type was 47,XXY(108 cases),followed by 47,XXX(80 cases)and 47,XYY(68 cases).Totally,18 cases were 45,X.Totally,51 cases were determined as chimera.The results of FISH in 862 cases(862/884)were consistent with those of karyotype analysis or CNV-seq,and the positive predictive value of FISH was 97.5%.A total of 24 cases were different from karyotype analysis,and CNV-seq was performed further.In the 22 cases,the results of CNV-seq were consistent with those of karyotype analysis,which could complement each other.The karyotype of 1 of the 2 inconsistent samples was 46,+mar,and the results of FISH and CNV-seq were 45,X.The karyotype analysis of 1 case showed that the heterochromatin region of chimeric Y chromosome was missing,the results of FISH and CNV-seq were chimeric,and the structure was not abnormal.Conclusions Combined determination of FISH and karyotype analysis is recommended when NIPS indicates chromosomal abnormalities,which can quickly and accurately diagnose chromosomal abnormalities.For suspected special structural abnormalities of chromosomes,FISH,karyotype analysis and CNV-seq combined determination is recommended to identify the genetic cause.