Chromosome Microarray Analysis Combined With Karyotype Analysis In Prenatal Diagnosis Of Fetuses With Increased NT

Purpose1.Investigate the use value of Chromosomal Microarray Analysis CMA in the neck transparent layer(nuchal translucency NT)to thicken fetal cases and whether it can replace karyotype analysis.2.Assess the differences detected by CMA technology in copy number variants CNVs in the following two groups:(1)Ultrasound indicates that fetal cases with NT thickening alone and fetal cases with NT thickening accompanied by other structural abnormalities(2)Senior and non-senile cases.3.Explore the application value of CMA technology in detecting chromosome microdeletions / microduplications.Method1.Research object: This study selects pregnant women from Inner Mongolia Maternal and Child Health Hospital from December 2017 to December 2019 during the early pregnancy check-up and color Doppler ultrasound to show that the fetal NT is thickened.The prenatal diagnosis clinic is recommended.For cases with fetal NT ≥3.0 mm,invasion is recommended Sexual prenatal examination,detection of chromosome karyotype and chromosome microarray analysis technology.Candidates have the conditions:(1)singleton;(2)refer to the measurement guidelines of the Fetal Medicine Foundation(FMF),measure the NT value at 11-13 + 6 weeks of pregnancy,and NT ≥ 3.0mm;(3)informed of the pregnant woman And signed to agree to join the study.2.Experimental method:2.1 Using the DNA extraction kit produced by Qiagen,the genomic DNA of the sample was extracted.2.2 Process the sample DNA according to the standard experimental operating procedures of the Affymetrix Cytoscan 750 K Array chip platform in the United States.2.3 For the files scanned by the chip,the AGCC Scan Control application program supporting the experiment is used to transform the information and analyze the data.2.4 According to the data of the existing database,compare and analyze the CMA test results to obtain the properties of CNVs.2.5 The X2 test in the statistical software SPSS 22.0 was selected to compare the differences in the detection rate of CNVs.When P <0.05 was specified,the difference was statistically significant.Results1.Results of karyotype analysis:Chromosome karyotype analysis results: a total of 185 cases of NT thickening,including 146 cases with normal karyotype,39 cases with abnormal karyotype,the incidence of chromosome abnormalities was 21.08%(39/185);34 of them were 21 Three cases,three cases were 18 cases,one case was 46,XN,del(8)(P21)and8p23.3del 2036Kb(VOUS)in CMA,8p23.2p21.1 dup 25.3Mb(LP)were the same case;one case : 46,XN,t(15;17)(q15;q25)[4] / 46,XN [122],CMA is 46,XN.2.CMA results:2.1 A total of 185 cases of NT thickening,including 126 cases with normal chromosomes and 59 cases with chromosomal abnormalities,the incidence of chromosomal abnormalities was 31.89%(59/185);40 of them had abnormal chromosome numbers(35 cases were trisomy 21).3 cases were trisomy 18,1 case was14 UPD,1 case was 47,XXX);19 cases were abnormal chromosome structure.2.2 The detection of microdeletions /microduplications is an increase of 10.81%(20/185)compared with karyotype analysis.The detection rate of pathogenic CNVs increased by 6.49%(12/185).2.3 There were 128 cases of NT in 0.3-0.4cm,including 38 cases of chromosomal abnormalities,accounting for 29.68%,36 cases of 0.41-0.5cm,of which 13 cases of chromosomal abnormalities accounted for 36.11%,0.5-1.6cm cases There were 21 and8 had chromosomal abnormalities,accounting for 38.10%.Conclusion1.The common genetic cause of NT abnormality is fetal chromosomal abnormality,which is most closely related to trisomy 21.The greater the thickness of NT,the greater the probability of abnormal chromosomes.2.Compared with karyotype analysis technology,CMA technology has the advantages of full genome high resolution of CMA technology.It can increase the detection rate of microdeletions / microduplications by an additional 10.81%(20/185),and increase the detection rate of pathogenic CNVs by 6.49%(12/185).In this experiment,2 cases of chimeras were detected by karyotype analysis,one case of CMA gave more accurate results,and one case was not detected(the final karyotype analysis result is considered clinically meaningless).Because CMA cannot recognize equilibrium rearrangement(translocation/inversion/insertion).CMA technology cannot temporarily replace karyotype analysis for diagnosis.3.The detection rate of CMA chromosome abnormality is higher in fetuses with other ultrasound abnormalities than NT alone,which is statistically significant.Therefore,fetuses with thickened NT and other structural abnormalities choose CMA technology for prenatal diagnosis of CNVs.Compared with non-elderly pregnant women,the odds of abnormal detection of CMA were not statistically significant.Therefore,there was no difference in the detection rate of abnormalities of CMA among age-increasing NT cases.4.In the detection of microdeletions / microduplications by CMA,there were 7 cases whose clinical significance was not clear VOUS(35%).The presence of VOUS would bring difficulties to the interpretation of CMA.But with the improvement of our cognitive level,the improvement of the database,the improvement of technology,and the reduction of VOUS is just around the corner.