| Objective To detect the ultrasonic abnormal fetuses using chromosomal microarray analysis(CMA),to explore and evaluate the application value of CMA in the prenatal diagnosis of ultrasonic abnormal fetuses.Methods 412 cases of fetuses with ultrasonic anomalies were included.After their parents were fully informed,the amniotic fluid samples or tissue samples from the aborted fetuses were collected for CMA.Comprehensive analysis and classified counting were done based on the test results.Results 31 cases(7.52%)with abnormal chromosome aneuploidies,41cases(9.95%)with pathogenetic CNVs and 2 cases(0.49%)with loss of heterozygosity were detectedin the 412 fetuses.The abnormal detection rate was 17.96%.Among all the cases,28 fetuses carried pathogenic CNVs smaller than 10 Mb,which represents a 7.28% higher detection rate of CMA compared to conventional karyotype analysis.In this study,we found the detection rate of fetuses in amniotic fluid samples was 13.01%,however,the detection rate of fetuses in muscle samples was 25.30%.The detection rates were significantly different between the two groups(chi-square test P<0.05).According to the number of ultrasound abnormalities,the detection rates were 10.30%,17.65%,27.91% and 58.82% in the single anomaly group,two anomalies groups,three anomalies groups,and four or more anomalies group respectively.The detection rates of each of the four groups were significantly different.In addition,there is a significant tendency of increasing from group 1 to group 4(Chi-square test P<0.001,Linear-by-Linear Association P<0.001).We divided all samples into three groups,including pure soft markers,amniotic fluid volume,umbilical blood flow anomaly group;isolated structural anomaly group and mixed group whose the detection rates were 4.32%?18.93% and 29.51% respectively.Among three groups,the detection rates were significantly different,in additions,the detection rates linearly increased(Chi-square test P<0.001,Linear-by-Linear Association P<0.001).In this study,we found the detection rate of aneuploidy of fetuses in amniotic fluid samples was 3.25%,however,the detection rate of aneuploidy of fetuses in muscle samples was 13.86%.The detection rates of aneuploidy were significantly different between the two groups(chi-square test P P<0.001).The detection rates of aneuploidy were 2.58%?5.88%?11.63% and 41.18% in the single anomaly group,two anomalies groups,three anomalies groups,and four or more anomalies group respectively.In each of the four groups,the detection rates of aneuploidy were significantly different.In addition,there is a significant tendency of increasing from group 1 to group 4(Chi-square test P<0.001,Linear-by-Linear Association P<0.001).In these groups,including pure soft markers,amniotic fluid volume,umbilical blood flow anomaly group;isolated structural anomaly group and mixed group,the detection rates of aneuploidy were 1.41%?7.45% and 14.75% respectively.Among three groups,the detection rates of aneuploidy were significantly different,in additions,the detection rates of aneuploidy linearly increased(Linear-by-Linear Association P<0.05,Chi-square test P<0.05).The risk of aneuploidy is increasing along with the terms or severity of ultrasonic anomalies;There is no significant association between the risk of PCNVs and the terms or severity of ultrasonic anomalies.Conclusions Compared to conventional karyotype analysis,CMA tests can prominently increase the detection rate of genetic abnormities in prenatal diagnosis of ultrasonic abnormal fetuses.The risk of chromosomal abnormities and the risk of aneuploidy increase along with the terms and the severity of the ultrasonic anomalies.Meanwhile there is no significant association between PCNVs detection rate and the terms and the severity of the ultrasonic anomalies,suggesting the necessity of CMA to all fetuses with ultrasonic anomalies.Therefore,the application of CMA in the prenatal diagnosis of ultrasonic abnormal fetuses should be further popularized.A fetus could obtain a derivative chromosome from parents with chromosomal balanced translocation.Therefore,for fetuses with deletion and duplication involving multiple chromosomes,parents' genetic tests are suggested,in order to define the origins of the chromosome anomalies and then support guidance for their next pregnancy.For fetuses with LOH region,parents' CMA test is also suggested.Using SNP calls supported by CMA,linkage analysis can be done to determine LOH origin,and,by comparing with the known imprint gene in this region,the pathogenicity of the LOH can be definite. |
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