低深度全基因组测序技术诊断先天性心脏病胎儿染色体变异病因价值

Value of copy number variation sequencing in the etiological diagnosis of fetus with congenital heart disease

目的:观察低深度全基因组测序(CNV-Seq)技术诊断先天性心脏病胎儿染色体变异病因价值.方法:经2位超声医师行胎儿超声心动图检查确诊胎儿患有先天性心脏病(CHD)孕妇80例,超声引导下经腹抽取羊水(孕16~24周)或脐带血(孕周>24周),分别行G-显带染色体核型分析及CNV-Seq检测.统计两种技术的检出阳性率.结果:80例CHD胎儿染色体核型分析检出8例异常核型,检出率为10.0%,分别是21-三体综合征4例、18-三体综合征3例,46,XX,der(6)(q16q22)1例,该结果与CNV-Seq检测结果一致.染色体核型分析结果72例胎儿中,CNV-Seq检出10例致病性拷贝数变异,检出率13.8%,1例临床意义未明的拷贝数变异,检出率为1.4%.结论:CNV-Seq能检测出CHD胎儿常规的染色体数目和结构异常,还可以检测到染色体片段微缺失微重复信息,提高诊断价值,为遗传学咨询提供依据.

Objective: To observe the value of copy number variation sequencing(CNV-Seq)in the etiological diagnosis of fetal congenital heart disease. Methods: 80 pregnant women with fetal congenital heart disease(CHD)confirmed through echocardiography examined by 2 ultrasound doctors were included in this study. 30 ml amniotic fluid(during 16-24 gestational weeks)or 2 ml umbilical cord blood(more than 24 gestational weeks) of these women were transabdominal extracted under the guidance of ultrasound, and were detected by G-banding chromosome karyotype analysis and CNV-Seq. The positive detection rates of the two techniques were summarized and counted. Results: There were 8 women with abnormal fetal karyotypes in the 80 women with fetal CHD after karyotype analysis of fetus, with the detection rate of 10.0%, which included 4 cases with trisomy 21 syndrome of fetus, 3 cases with trisomy 18 syndrome of fetus, and 1 case with 46, XX, DER(6)(Q16 Q22) of fetus, and the results of which was consistent with the results of CNV-Seq detection. In 72 fetuses after karyotype analysis, there were 10 cases with pathogenic copy number variation of fetal chromosome, with the detection rate of 13.8%, and there was 1 case with 1 unknown clinical copy number variation, with the detection rate of 1.4%. Conclusion: CNV-Seq can not only detect the conventional chromosome number and structural abnormalities of fetal CHD,but also can detect the microdeletion and microduplication information of chromosome fragment, which can increase the diagnostic value and can provide the evidences for genetics counseling.