拷贝数变异测序在检测胎儿鼻骨发育不良结果中的应用研究

Application of copy number variation sequencing in detecting fetal nasal bone dysplasia

摘要

目的 探讨拷贝数变异测序(CNV-seq)应用在胎儿鼻骨发育结果检测的临床价值。方法 选取2018年8月至2019年12月在广州市妇女儿童医疗中心柳州医院进行产前超声筛查发现胎儿鼻骨发育异常的孕妇160例为研究对象,比较染色体核型分析和CNV-seq技术检测结果差异。结果 染色体核型分析检测出39例染色体异常,其中常染色体数目异常32例,性染色体异常5例,染色体结构异常2例;CNV-seq检测出16例染色体异常,其中多态性9例,明确致病性7例;年龄≥35岁孕妇羊水染色体核型异常检出率高于年龄<35岁孕妇,且在年龄≥35岁孕妇中,羊水染色体核型异常检出率高于CNV-seq检测(χ²值分别为15.856、20.928,P<0.05);胎龄<24周羊水染色体核型异常检出率高于胎龄≥24周,且在胎龄<24周中,羊水染色体核型异常检出率高于CNV-seq检测(χ²值分别为16.979、16.311,P<0.05);产前诊断指征2项及以上者羊水染色体核型异常检出率高于2项以下者,而CNV-seq异常检出率明显低于2项以下者(χ²值分别为9.246、10.338,P<0.05);在产前诊断指征2项及以上者中,羊水染色体核型异常检出率高于CNV-seq检测(χ²=27.655,P<0.05)。结论 在产前超声筛查出胎儿鼻骨发育异常的孕妇中,CNV-seq有较好的应用价值,可弥补染色体核型分析的不足,有助于染色体结构异常的检出.

Abstract

Objective To explore clinical value of copy number variation sequencing (CNV-seq) in detecting fetal nasal bone dysplasia. Methods 160 pregnant women who underwent prenatal ultrasound screening and were found to have abnormalities in fetal nasal bone development in Liuzhou Hospital of Guangzhou Women and Children's Medical Center from August 2018 to December 2019 were selected as research subjects. The differences in detection rate of chromosome abnormalities by chromosome karyotype analysis and by CNV-seq were compared. Results Chromosome karyotype analysis shown that 39 cases of chromosome abnormalities were found, including 32 cases of abnormal number of autosomes, 5 cases of abnormal sex chromosomes and 2 cases of chromosomal structural abnormalities. CNV-seq shown that 16 cases of chromosome abnormalities were found, including 9 cases of polymorphisms and 7 cases of confirmed pathogenic CNVs. The detection rate of amniotic fluid chromosome abnormalities in the pregnant women aged ≥35 years was higher than that in those pregnant women aged <35 years, and among the pregnant women aged ≥35 years, the detection rate of amniotic fluid chromosome abnormalities by chromosome karyotype analysis was higher than that by CNV-seq (χ²=15.856 and 20.928 respectively, both P<0.05). The detection rate of amniotic fluid chromosome abnormalities by chromosome karyotype analysis was higher in the pregnant women with gestational age <24 weeks than that in those pregnant women with gestational age ≥24 weeks, and in those pregnant women with gestational age <24 weeks, the detection rate of chromosome abnormalities in amniotic fluid by chromosome karyotype analysis was higher than that by CNV-seq (χ²=16.979 and 16.311 respectively, both P<0.05). The detection rate of amniotic fluid chromosome abnormalities by chromosome karyotype analysis in the pregnant women with 2 or more prenatal diagnostic indications was higher than that in those pregnant women with less than 2 prenatal diagnostic indications, while by CNV-seq, the detection rate of chromosome abnormalities in the pregnant women with 2 or more prenatal diagnostic indications was significantly lower than that in those pregnant women with less than 2 prenatal diagnostic indications (χ²=9.246 and 10.338 respectively, both P<0.05). Among the pregnant women with 2 or more indications for prenatal diagnosis, the detection rate of amniotic fluid chromosome abnormalities was higher than that by CNV-seq (χ²=27.655, P<0.05). Conclusion CNV-seq has good application value in the pregnant women who were found to have developmental abnormalities of fetal nasal bone found in prenatal ultrasound screening, which can compensate for shortcomings of chromosome karyotype analysis and help to identify those chromosomal structural abnormalities.

关键词

拷贝数变异测序 / 染色体核型分析 / 胎儿 / 鼻骨发育不良 / 应用价值

Key words

copy number variation sequencing / chromosome karyotype analysis / fetus / nasal bone dysplasia / application value

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基金资助

广西壮族自治区卫生健康委员会科研课题(Z20180032)

广西科技计划项目(广西妇产科疾病临床医学研究中心)(桂科AD22035223)