Evaluation the Application of Karyotype Analysis and Chromosome Microarray in Prenatal Diagnosis
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Abstract
Background: We aimed to compare the difference of the chromosomal abnormalities using karyotype analysis and chromosomal microarray (CMA) as well as to evaluate their application in different prenatal diagnosis indications.
Methods: Overall, 3007 pregnant women with prenatal diagnosis indications from Medical Genetics Department of Linyi Women and Children’s Health Care Hospital, who underwent standard G-banded karyotype analysis and CMA, were enrolled from 2018-2022. G-banded karyotype analysis and CMA were undergone simultaneously. All fetuses with genetic variants were enrolled for further analyzing. The frequency and differences of chromosomal abnormalities of the two methods were compared in different prenatal diagnosis indications groups.
Results: CMA improved 4.09% (123/3007) of genetic changes compared karyotype analysis. CMA is on par with karyotyping for detection of aneuploidies and gross unbalanced rearrangements. Serological screening and ultrasound abnormalities were the main indications of prenatal diagnosis. The detection rate of chromosomal abnormalities was highest in non-invasive prenatal testing (NIPT) abnormal group. In the ultrasound abnormality group, the detection rate of genetic variants in nuchal translucency (NT) increased group was higher than other subgroups and there was statistically significant difference in the detection rate of pCNVs. CMA can detect 5.57% (40/718) more genetic abnormalities in ultrasound abnormality group on the normal karyotype. CMA improved 0.67% (20/3007) of genetic changes with clinically significant compared karyotype, brought 3.42% (103/3007) of variants with uncertain significance (VOUS).
Conclusion: CMA identified additional, clinically significant genetic variants on the basis of normal karyotype analysis, brought a proportion of unclear significant variants. All the pregnant women accepted amniocentesis should be informed about their characteristics of karyotype analysis and CMA by genetic counselors.
2. Xia M, Yang X, Fu J, et al (2020). Applica-tion of chromosome microarray analysis in prenatal diagnosis. BMC Pregnancy Childbirth, 20(1):696.
3. Burke W, Parens E, Chung WK, et al (2022). The Challenge of Genetic Variants of Uncertain Clinical Significance: A Narra-tive Review. Ann Intern Med, 175(7):994-1000.
4. American College of Obstetricians and Gy-necologists Committee on Genetics (2013). Committee Opinion No. 581: the use of chromosomal microarray analysis in prenatal diagnosis. Obstet Gynecol, 122(6):1374-1377.
5. Levy B, Wapner R (2018). Prenatal diagnosis by chromosomal microarray analysis. Fer-til Steril, 109(2):201-212.
6. Hu T, Tian T, Zhang Z, et al (2021). Prenatal chromosomal microarray analysis in 2466 fetuses with ultrasonographic soft mark-ers: a prospective cohort study. Am J Ob-stet Gynecol, 224(5):516.e1-516.e16.
7. Wapner RJ, Martin CL, Levy B, et al (2012). Chromosomal microarray versus karyo-typing for prenatal diagnosis. N Engl J Med, 367(23):2175-2184.
8. Batzir NA, Shohat M, Maya I (2015). Chro-mosomal Microarray Analysis (CMA) a Clinical Diagnostic Tool in the Prenatal and Postnatal Settings. Pediatr Endocrinol Rev, 13(1):448-454.
9. Burke W, Parens E, Chung WK, et al (2022). The Challenge of Genetic Variants of Uncertain Clinical Significance: A Narra-tive Review. Ann Intern Med, 175(7):994-1000.
10. Portnoï MF (2009). Microduplication 22q11.2: a new chromosomal syndrome. Eur J Med Genet, 52(2-3):88-93.
11. Wentzel C, Fernström M, Ohrner Y, et al (2008). Clinical variability of the 22q11.2 duplication syndrome. Eur J Med Genet, 51(6):501-510.
12. Li J, Hojlo MA, Chennuri S, et al (2021). Underrepresentation of Phenotypic Vari-ability of 16p13.11 Microduplication Syn-drome Assessed With an Online Self-Phenotyping Tool (Phenotypr): Cohort Study. J Med Internet Res, 23(3):e21023.
13. Jønch AE, Douard E, Moreau C, et al (2019). Estimating the effect size of the 15Q11.2 BP1-BP2 deletion and its con-tribution to neurodevelopmental symp-toms: recommendations for practice. J Med Genet, 56(10):701-710.
14. Naqvi M, Goldfarb IT, Hanmer KJ, et al (2016). Chromosomal microarray use among women undergoing invasive pre-natal diagnosis. Prenat Diagn, 36(7):656-661.
15. Oneda B, Rauch A (2017). Microarrays in prenatal diagnosis. Best Pract Res Clin Ob-stet Gynaecol, 42:53-63.
16. Kang H, Wang L, Li X, et al (2022). Applica-tion of chromosome microarray analysis and karyotyping in diagnostic assessment of abnormal Down syndrome screening results. BMC Pregnancy Childbirth, 22(1):813.
17. Hu Y, Liu W, He G, et al (2022). Clinical util-ity of expanded NIPT for chromosomal abnormalities and etiology analysis of cy-togenetic discrepancies cases. J Assist Re-prod Genet, 39(1):267-279.
18. Callaway JL, Shaffer LG, Chitty LS, et al (2013). The clinical utility of microarray technologies applied to prenatal cytoge-netics in the presence of a normal con-ventional karyotype: a review of the litera-ture. Prenat Diagn, 33(12):1119-1123.
19. de Wit MC, Srebniak MI, Govaerts LC, et al (2014). Additional value of prenatal ge-nomic array testing in fetuses with isolat-ed structural ultrasound abnormalities and a normal karyotype: a systematic re-view of the literature. Ultrasound Obstet Gy-necol, 43(2):139-146.
20. Hao M, Li L, Zhang H, et al (2020). The dif-ference between karyotype analysis and chromosome microarray for mosaicism of aneuploid chromosomes in prenatal diagnosis. J Clin Lab Anal, 34(12):e23514.
21. Wang J, Wang D, Yin Y, et al (2022). As-sessment of Combined Karyotype Anal-ysis and Chromosome Microarray Analy-sis in Prenatal Diagnosis: A Cohort Study of 3710 Pregnancies. Genet Res (Camb), 2022:6791439.
| Files | ||
| Issue | Vol 53 No 4 (2024) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijph.v53i4.15560 | |
| Keywords | ||
| Prenatal diagnosis Chromosome microarray analysis Karyotype analysis Genetic variant | ||
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