Potentials and challenges of chromosomal microarray analysis in prenatal diagnosis

Abstract

Introduction: For decades, conventional karyotyping analysis has been the gold standard for detecting chromosomal abnormalities during prenatal diagnosis. With the development of molecular cytogenetic methods, this situation has dramatically changed. Chromosomal microarray analysis (CMA), a method of genome-wide detection with high resolution, has been recommended as a first-tier test for prenatal diagnosis, especially for fetuses with structural abnormalities.Methods: Based on the primary literature, this review provides an updated summary of the application of CMA for prenatal diagnosis. In addition, this review addresses the challenges that CMA faces with the emergence of genome sequencing techniques, such as copy number variation sequencing, genome-wide cell-free DNA testing, and whole exome sequencing.Conclusion: The CMA platform is still suggested as priority testing methodology in the prenatal setting currently. However, pregnant women may benefit from genome sequencing, which enables the simultaneous detection of copy number variations, regions of homozygosity and single-nucleotide variations, in near future.

Chromosomal Microarray Analysis for Prenatal Diagnosis of Uniparental Disomy: A Retrospective Study

“…Karyotype and CMA analysis are two prenatal diagnostic methods that have been widely used in recent years [15][16][17] . As molecular cytogenetic methods have advanced, Chromosomal Microarray Analysis (CMA) has gained prominence and is now suggested as a primary diagnostic test for prenatal assessments.The potential of CMA and the challenges, when compared to conventional karyotyping, are discussed below [3] .However, CMA cannot detect balanced translocations and inverted mosaicism. Karyotype analyses and SNP-arrays have their own advantages and limitations for the diagnosis of mosaicisms and the combination of these methods provides a rigorous diagnosis [15,16] .…”

“…CMA is a genomic hybridization method that is superior to karyotype analysis, but CMA is unable to detect balanced recombinations and is more expensive [2] . However, pregnant women may also bene t from CMA method, which enables the simultaneous detection of copy number variations, ROH and SNPs [3] . Uniparental disomy (UPD) refers to the inheritance of both homologous chromosomes within a chromosome pair from a single parent.…”

The Role of Thickened Nuchal Translucency on Copy Number Variations and Pregnancy Outcomes in Northeast Coast of Fujian Province, China: A Comparison Between Traditional Karyotyping and Single Nucleotide Polymorphism Array Analysis

“…CMA is a high-resolution method for genome-wide detection and is recommended as the primary test for prenatal diagnosis [18,19]. This method can be used to detect the CNVs of chromosomal imbalances such as aneuploidy and unbalanced rearrangements, particularly chromosome microdeletions and duplications [12]. With a normal karyotype, CMA can detect approximately 1% clinically signi cant microdeletions/microduplications in structurally normal pregnancies and 6% structural anomalies in prenatal diagnostic cases [20].…”

“…Chromosomal microarray analysis (CMA) is used to detect CNVs in the whole genome. This method can be used to detect CNVs of chromosome imbalances, such as aneuploidy and unbalanced rearrangements, particularly chromosome microdeletions and duplications that cannot be detected using standard karyotyping [12,13].…”

Chromosomal microarray analysis for prenatal diagnosis of uniparental disomy: a retrospective study

“…CMA is a genomic hybridization method that is superior to karyotype analysis, but it cannot detect balanced recombination and is more expensive [ 22 ]. However, pregnant women may also benefit from CMA method, which enables the simultaneous detection of copy number variations, ROH and SNPs [ 19 ]. There are three scenarios in which ROH appears in the prenatal sample: (a) Indication of UPD: when a ROH of > 10 Mb occurred on a single chromosome of a fetus (at the end of the chromosome, ROH > 5 Mb,not at the end of the chromosome, ROH > 10 Mb), (b) Identity of descent: ROH > 10 Mb appears on multiple chromosomes, indicating a close parental relationship (the closer the relationship, the more ROH regions), (c) Common ancestral markers in populations.…”