Comparison of karyotype analysis and SNP-array in prenatal diagnosis of mosaicism aneuploidy

2021 ◽  
Author(s):  
Ting Wang ◽  
Huamei Huang ◽  
Lihua Wu ◽  
Yanlin Huang ◽  
Xianzheng Li ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Amniotic Fluid ◽  
Cord Blood ◽  
Chromosomal Abnormalities ◽  
Karyotype Analysis ◽  
Snp Array ◽  
Chorionic Villi ◽  
Advantages And Disadvantages ◽  
Positive Rate ◽  
The Difference

Abstract Objective To determine the best method for chromosome detection of mosaicism by comparing the results of karyotype and SNP-array in amniotic fluid,chorionic villi and cord blood. Methods A total of 14,805 pregnant women underwent invasive prenatal diagnosis.SNP-array and karyotype analysis were used to detect chromosomal abnormalities. Results A total of 169 cases of mosaicism were detected in this study.Mosaicism was found in both karyotype and SNP-array in 99(0.66%,99/14,805) cases of prenatal samples. In the remaining 70 cases of mosaicism, the results of karyotype and SNP-array were discrepant with ten cases(1.04%,10/959),forty-five cases (0.5%,45/9034) and fifteen cases(0.31%,15/4812) dectected from CV,AF and CB respectively. The mosaic positive rate of karyotype analysis only was 1.11%(164/14,805), which was significantly higher than that of SNP-array (0.7%,104/14,805), and the difference was statistically significant (P < 0.001). The mosaic positive rate of combination with SNP-array and karyotype was 1.14%(169/14,805), which was higher than that of SNP-array(0.7%). Conclusions This study demonstrated that the combination of SNP-array and karyotype analysis may be the best strategy for the prenatal diagnosis of mosaicism aneuploidy.These two techniques have their own advantages and disadvantages, which can complement each other in clinical application.

scholarly journals Clinical Utility and the Yield of Single Nucleotide Polymorphism Array in Prenatal Diagnosis of Fetal Central Nervous System Abnormalities

2021 ◽  
Vol 8 ◽  
Author(s):  
Meiying Cai ◽  
Hailong Huang ◽  
Liangpu Xu ◽  
Na Lin
Keyword(s):  
Central Nervous System ◽  
Single Nucleotide Polymorphism ◽  
Copy Number ◽  
Chromosomal Abnormalities ◽  
Karyotype Analysis ◽  
Snp Array ◽  
Copy Number Variations ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Pathogenic Cnvs

Applying single nucleotide polymorphism (SNP) array to identify the etiology of fetal central nervous system (CNS) abnormality, and exploring its association with chromosomal abnormalities, copy number variations, and obstetrical outcome. 535 fetuses with CNS abnormalities were analyzed using karyotype analysis and SNP array. Among the 535 fetuses with CNS abnormalities, chromosomal abnormalities were detected in 36 (6.7%) of the fetuses, which were consistent with karyotype analysis. Further, additional 41 fetuses with abnormal copy number variations (CNVs) were detected using SNP array (the detection rate of additional abnormal CNVs was 7.7%). The rate of chromosomal abnormalities, but not that of pathogenic CNVs in CNS abnormalities with other ultrasound abnormalities was significantly higher than that in isolated CNS abnormalities. The rates of chromosomal abnormalities and pathogenic CNVs in fetuses with spine malformation (50%), encephalocele (50%), subependymal cyst (20%), and microcephaly (16.7%) were higher than those with other isolated CNS abnormalities. The pregnancies for 36 cases with chromosomal abnormalities, 18 cases with pathogenic CNVs, and three cases with VUS CNVs were terminated. SNP array should be used in the prenatal diagnosis of fetuses with CNS abnormalities, which can enable better prenatal assessment and genetic counseling, and affect obstetrical outcomes.

scholarly journals Chromosomal Microarray Analysis of Fetuses with Nasal Bone Anomaly

2020 ◽  
Author(s):  
Xiaorui Xie ◽  
Xiaoqing Wu ◽  
Linjuan Su ◽  
Meiying Cai ◽  
Ying Li ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Prenatal Diagnosis ◽  
Chromosomal Abnormalities ◽  
Snp Array ◽  
Nasal Bone ◽  
Chromosomal Microarray Analysis ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Fetal Nasal Bone ◽  
Structural Abnormalities

Abstract Objective: To explore the significance and value of fetal nasal bone anomaly (absence or hypoplasia) as indications of prenatal diagnosis.Methods: A total of 102 fetuses diagnosed with nasal bone absence or hypoplasia by ultrasonography underwent chorionic, amniotic, or umbilical cord blood puncture. Single nucleotide polymorphism microarray (SNP-array) was used to analyze fetal chromosomes.Results: Of the 102 fetuses with nasal bone absence or hypoplasia, 25 (24.5%) had chromosomal abnormalities, including 15 cases of trisomy 21, one trisomy 18 case, and 9 cases of other copy number variations. Among the 52 cases with isolated nasal bone absence or hypoplasia, 7(13.5%) had chromosomal abnormalities. In 50 cases, abnormal nasal bone with additional soft markers or structural abnormalities was observed, while 18 cases (36.0%) had chromosomal abnormalities, which were significantly higher than that among the fetuses with isolated nasal bone abnormality.Conclusion: Fetal nasal bone absence or hypoplasia can be used as an indication for prenatal diagnosis. The detection rate of chromosomal abnormalities increases with additional soft markers or structural abnormalities. This study demonstrates that fetal nasal bone absence or hypoplasia is associated with micro-deletions or micro-duplications of chromosomes. Application of single nucleotide polymorphism microarray (SNP-array) technology can reduce the rate of missed prenatal diagnoses.

scholarly journals The Genetic Etiology Diagnosis of Fetal Growth Restriction Using Single-Nucleotide Polymorphism-Based Chromosomal Microarray Analysis

2021 ◽  
Vol 9 ◽  
Author(s):  
Yu'e Chen ◽  
Yingjun Xie ◽  
Yuying Jiang ◽  
Qi Luo ◽  
Lijing Shi ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Microarray Analysis ◽  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Detection Rate ◽  
Chromosomal Abnormalities ◽  
Karyotype Analysis ◽  
Growth Restriction ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis

Background: An increase in pathogenic copy number variants (pCNVs) has been recognized to associate with fetal growth restriction (FGR). Here, we aim to explore the application value of chromosomal microarray analysis (CMA) in prenatal diagnosis of FGR.Methods: Prenatal ultrasound was applied to identify FGR. A total of 149 pregnant women with FGR were enrolled in our study. All subjects underwent karyotype analysis and CMA to reveal the chromosomal abnormalities.Results: In this study, all subjects were successfully detected by karyotype and CMA analyses. Of these subjects, the chromosomal abnormalities detection rate was 5.37% (8/149) for karyotyping and 13.42% (20/149) for CMA, respectively. Among them, an 8.05% (12/149) incremental yield of CMA over karyotype analysis was observed (p = 0.004). In addition, a significant difference of pCNV detection rate was observed between the groups with different high-risk factors (p = 0.005). The FGR with structural anomalies group showed the highest pCNV detection rate (33.33%), followed by the FGR with non-structural anomalies group (8.77%) and the isolated FGR group (8.06%).Conclusion: In conclusion, CMA technology showed an effective application value in etiology diagnosis of FGR. We believe that CMA should be recommended as first-line detection technology for prenatal diagnosis in FGR.

scholarly journals Application of the BACs-on-Beads assay for the prenatal diagnosis of chromosomal abnormalities in Quanzhou, China

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jianlong Zhuang ◽  
Chunnuan Chen ◽  
Yuying Jiang ◽  
Qi Luo ◽  
Shuhong Zeng ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
High Risk ◽  
Chromosomal Abnormalities ◽  
Karyotype Analysis ◽  
Prenatal Testing ◽  
High Risk Group ◽  
Success Rates ◽  
High Detection Rate ◽  
High Risk Factors ◽  
Initial Objective

Abstract Background An increasing number of techniques have been used for prenatal diagnosis of genetic abnormalities. Our initial objective was to explore the value of the BACs-on-Beads (BoBs) assay for the prenatal diagnosis of aneuploidies and microdeletion/microduplication syndromes in Quanzhou, Southeast China. Methods A total of 1409 pregnant women with high-risk factors for chromosomal abnormalities admitted to Quanzhou Women’s and Children’s Hospital were enrolled in this study. BoBs assays and karyotype analyses were conducted for all subjects. Subsequently, chromosome microarray analysis (CMA) or fluorescence in situ hybridization (FISH) was performed to validate the findings. Results In this study, karyotype analysis and BoBs assay failed in 4 cases, and 2 cases, respectively. A total of 1403 cases were successfully analyzed, with success rates of 99.72% (1405/1409) and 99.85% (1407/1409) for karyotype analysis and Bobs assay, respectively. BoBs assay rapidly detected chromosomal aneuploidies in line with the karyotyping data. Additionally, 23 cases of microdeletions/microduplications were detected by BoBs assay but missed by karyotyping, including 22q11.2 microdeletions/microduplications, 5p15.32p15.33 microdeletion, Xp22.31 microdeletions/microduplications, Xq27.3 microdeletion, and Yp11.2 and Yq11.22q11.222 microduplication. In comparison with karyotyping, fewer mosaicisms were identified by BoBs assay. A high detection rate of chromosomal abnormalities was observed in the high-risk group during noninvasive prenatal testing (NIPT) (41.72%) and the abnormal ultrasound group (13.43%). Conclusions BoBs assay can be used for the rapid and efficient prenatal diagnosis of common aneuploidies and microdeletion/microduplication syndromes. Moreover, the combined use of BoBs assay and karyotyping in prenatal diagnosis may allow for a more effective detection of chromosomal abnormalities.

scholarly journals Advances in the prenatal diagnosis of hematologic diseases

Blood ◽  
1984 ◽  
Vol 64 (2) ◽  
pp. 329-340 ◽  
Author(s):  
BP Alter
Keyword(s):  
Prenatal Diagnosis ◽  
Molecular Biology ◽  
Amniotic Fluid ◽  
Molecular Probes ◽  
Gene Products ◽  
Fetal Blood ◽  
Hematologic Disease ◽  
Chorionic Villi ◽  
Hematologic Diseases ◽  
Amniotic Cells

Abstract Prenatal diagnosis of hematologic diseases can now be performed with fetal blood, fetal amniotic fluid cell DNA, and fetal chorionic villi DNA. Some hemoglobinopathies can be detected by all three methods, and the choice will depend on the available obstetric and laboratory techniques, as well as the time of presentation of the pregnancy. Hopefully, further development of molecular probes and techniques will soon expand these options to all of the globin disorders. Detection of coagulation disorders in utero currently requires samples of pure fetal blood. Gene cloning is accomplished for some (factor IX and antithrombin III) and is underway for others (factor VIII), and further investigation is necessary to determine whether deficiencies in these gene products are due to gene deletion or to mutant genes linked to polymorphic restriction enzyme sites of diagnostic use. Thus, molecular biology may be applied to prenatal diagnosis of the clotting problems, but this has not yet been accomplished. Disorders affecting the number and/or function of erythrocytes, leukocytes, and platelets can be diagnosed by analysis of fetal blood. Blood samples will continue to be required until more is known about the molecular biology of hematopoiesis. Syndromes that can be diagnosed by chromosome studies should be revealed in cultures of amniotic fluid cells, fetal blood lymphocytes, and chorionic villi cells. Cultured cells can be examined for karyotypes, Y-chromatin, spontaneous or induced chromosome breakage, DNA repair, SCEs, and translocations. The techniques for culturing amniotic cells and fetal blood white cells are established, and those for growing cells from chorionic villi are improving rapidly. Direct preparations of cells from villi only may suffice for some of the above analyses. The study of hematologic disease in utero has thus come full circle, from the use of amniotic cells to determine the sex in X-linked disorders, to fetal blood sampling for the analysis of gene products, then back to amniocentesis for DNA, and now earlier in gestation to chorionic villi. All of this has occurred in less than ten years, and it is anticipated that developments in the next ten years will be equally dramatic. The future should bring all prenatal testing into the first trimester, use molecular probes, and provide for both early diagnosis and early treatment of genetic hematologic disease.

P–558 SNP array versus karyotype for prenatal diagnosis in fetuses with abnormal ultrasound: a systematic review and meta-analysis

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
V Kamath ◽  
M P Chacko ◽  
M Mariano ◽  
R Kirubakaran ◽  
M S Kamath
Keyword(s):  
Systematic Review ◽  
Single Nucleotide Polymorphism ◽  
Prenatal Diagnosis ◽  
Diagnostic Accuracy ◽  
Chromosomal Abnormalities ◽  
Snp Array ◽  
Index Test ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide

Abstract Study question Does Single nucleotide polymorphism (SNP) array provide a diagnostic advantage over conventional karyotype in prenatal diagnosis for fetuses with an abnormal ultrasound? Summary answer SNP array in the prenatal setting provides an incremental diagnostic yield over karyotype and the diagnostic accuracy is comparable with combined SNP array and karyotype What is known already Single nucleotide polymorphism and comparative genomic hybridization based arrays (aCGH) are the two chromosomal microarray (CMA) platforms available. Guidelines which recommend offering CMA instead of karyotyping for prenatal diagnosis are mainly based on studies that compared aCGH with karyotype. There is a paucity of reviews that critically appraise the role of SNP array as a prenatal diagnostic tool. We decided to estimate the incremental yield of SNP array over karyotype in detecting chromosomal abnormalities, and to determine the diagnostic accuracy of SNP alone compared with SNP array and karyotype in combination for prenatal diagnosis in fetuses with an abnormal ultrasound. Study design, size, duration We conducted a systematic review of studies comparing SNP array with karyotype for prenatal diagnosis in fetuses with an abnormal ultrasound. We performed a literature search in the electronic databases of EMBASE, PubMed, CENTRAL, CDSR, SCOPUS and Web of science for relevant studies published in the English language between January1996 and May 2020. We also hand searched the referenced list of included studies and performed a google search for grey literature to identify potential studies. Participants/materials, setting, methods The study population was women undergoing prenatal diagnosis for abnormal fetal ultrasound. Studies in which SNP array and karyotyping had been used in fetuses with abnormal ultrasound and which allowed for a 2 x 2 data extraction table were included. We estimated the incremental yields for SNP array over karyotype. For determining the diagnostic accuracy, we considered SNP array alone as the index test and combined karyotype & SNP array as the reference standard. Main results and the role of chance We included six studies for quantitative analysis. After pooling results, incremental yield of SNP array over normal karyotype was 10% (95% confidence interval, CI 4 to 16%) in fetuses with abnormal ultrasound while incremental yield of karyotype over SNP array was 1% (95% CI 0 to 2%). The agreement between SNP array and karyotype was 92%. Variant of uncertain significance (VUS) rates ranged from 4–8%. For SNP array alone versus combined SNP array and conventional karyotype, pooled sensitivity and specificity was 0.96 (95% CI 0.91 to 0.99) and 1.00 (95% CI 0.99 to 1.00) respectively. The Area under curve (AUC) was 0.99 indicating the discriminating ability of the SNP array was very high to identify the fetus with chromosomal abnormalities. Limitations, reasons for caution Only studies published in English were included. There was some degree of heterogeneity in inclusion criteria for the included studies. Wider implications of the findings: The current study suggests SNP array alone can replace conventional karyotype for prenatal diagnosis in fetus with an abnormal ultrasound. Limitations to adoption of SNP testing might include the requirement of requisite expertise to interpret the results and counsel patients appropriately, especially with the propensity of SNPs to identify VUS. Trial registration number Not applicable

scholarly journals Combined Application of Chromosome Karyotype and Microarray Analysis in Fetus With Increased Nuchal Translucency

2021 ◽  
Author(s):  
Wang Chaohong ◽  
Tang Junxiang ◽  
Sun Yuxiu ◽  
Pang Yu ◽  
Tong Keting ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Pregnant Women ◽  
Microarray Analysis ◽  
Chromosomal Abnormalities ◽  
Karyotype Analysis ◽  
Nuchal Translucency ◽  
Chromosome Abnormalities ◽  
Detection Rates ◽  
Combined Application ◽  
Chromosome Karyotype

Abstract Objective：To examine the risk of chromosomal abnormalities when the thickness of the nuchal translucency( NT ) is 2.5-2.9mm, to evaluate the cutoff value of NT for prenatal diagnosis, to explore the value of combined application of chromosome karyotype and microarray analysis, and to explore the relationship between NT ≥ 5.0mm and fetal prognosis. Methods：A total of 366 pregnant women who underwent prenatal diagnosis in Anhui Province Maternity and Child Health Hospital from January 2018 to August 2020 were collected, of which 241 cases had NT ≥ 2.5mm, 125 cases were elderly (35-38 years old) with NT < 2.5mm. We made grouping statistics on chromosome abnormalities,and compared the detection of chromosome abnormalities by karyotype and microarray analysis. At the same time, we followed up the fetuses with NT ≥ 5.0mm and analyzed their prognosis. Results: (1)Among the 366 cases with NT thickening,the detection rates of chromosome abnormalities by karyotype analysis and microarray analysis(CMA) were 13.39% (49/366) and 13.93% (51/366), respectively, and there was no significant difference (P>0.05), including 25 cases of trisomy 21, 5 cases of trisomy 18, 5 cases of Turner synthesis and 16 cases of other chromosome abnormalities. (2)We compared the effect of different NT value on the detection rate of pathogenic chromosomes, and found that the difference between NT ≥2.5mm and NT < 2.5mm was statistically significant(P<0.05). The detection rates of pathogenic chromosomal abnormalities in NT < 2.5mm group,2.5-2.9mm group, 3.0-3.4mm group,3.5-4.4mm group,4.5-5.4mm group and NT ≥ 5.5mm group were 0.8%(1/ 125), 11.63%(10/ 86), 17.81%(13/ 73), 20%(10/ 49), 47.62%(10/ 21) and 63.64%(7/ 11) respectively. (3)Our study found that different prenatal diagnostic indicators for abnormal chromosome detection rate difference was statistically significant(P<0.05). The detection rates of NT thickening alone and NT thickening combined with other abnormalities were 13.17%(22/ 167) and 35.14%(26/ 74) respectively(P<0.05). (4)Among 18 pregnant women with NT ≥ 5.0 mm, 9 fetuses were chromosomal abnormalities, and 9 fetuses survived healthily. Conclusions：When the NT value is 2.5-2.9mm, the incidence of fetal chromosome abnormality is significantly higher than that in the normal group. It is suggested that invasive prenatal diagnosis should be performed for pregnant women with NT ≥ 2.5mm. Chromosome karyotype analysis and CMA can complement each other, which is conducive to prenatal genetic counseling. The fetuses with NT thickening usually have good pregnancy outcomes when excluding fetal chromosome and prenatal ultrasound does not indicate any abnormalities.

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