Prenatal Diagnosis by Chromosome Microarray Analysis, An Indian Experience

Lall, Meena; Agarwal, Shruti; Paliwal, Preeti; Saviour, Pushpa; Joshi, Anju; Joshi, Arti; Mahajan, Surbhi; Bijarnia‐Mahay, Sunita; Puri, Ratna Dua; Verma, Ishwar C.

doi:10.1007/s13224-020-01413-6

Cited by 2 publications

(1 citation statement)

References 23 publications

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“…Previous studies have found that 2%–4% of RSA couples carry chromosomal abnormalities ( Fryns and Van Buggenhout, 1998 ; Popescu et al, 2018 ), but the actual number of chromosomal variants undetectable by routine karyotyping is much higher than that ( Dong et al, 2019 ). Compared with the low resolution of karyotyping, genome copy number variation sequencing (CNV-seq) and chromosomal microarray analysis (CMA) can detect copy number variations (CNVs) at submicroscopic level, which improves the detection of microdeletions/microduplications in abortion tissues ( Bajaj Lall et al, 2021 ). However, CNV-seq/CMA cannot detect balanced chromosomal abnormalities.…”

Section: Introductionmentioning

confidence: 99%

Analysis of chromosomal structural variations in patients with recurrent spontaneous abortion using optical genome mapping

Rao,

Zhang,

Zou

et al. 2023

Front. Genet.

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Background and aims: Certain chromosomal structural variations (SVs) in biological parents can lead to recurrent spontaneous abortions (RSAs). Unequal crossing over during meiosis can result in the unbalanced rearrangement of gamete chromosomes such as duplication or deletion. Unfortunately, routine techniques such as karyotyping, fluorescence in situ hybridization (FISH), chromosomal microarray analysis (CMA), and copy number variation sequencing (CNV-seq) cannot detect all types of SVs. In this study, we show that optical genome mapping (OGM) quickly and accurately detects SVs for RSA patients with a high resolution and provides more information about the breakpoint regions at gene level.Methods: Seven couples who had suffered RSA with unbalanced chromosomal rearrangements of aborted embryos were recruited, and ultra-high molecular weight (UHMW) DNA was isolated from their peripheral blood. The consensus genome map was created by de novo assembly on the Bionano Solve data analysis software. SVs and breakpoints were identified via alignments of the reference genome GRCh38/hg38. The exact breakpoint sequences were verified using either Oxford Nanopore sequencing or Sanger sequencing.Results: Various SVs in the recruited couples were successfully detected by OGM. Also, additional complex chromosomal rearrangement (CCRs) and four cryptic balanced reciprocal translocations (BRTs) were revealed, further refining the underlying genetic causes of RSA. Two of the disrupted genes identified in this study, FOXK2 [46,XY,t(7; 17)(q31.3; q25)] and PLXDC2 [46,XX,t(10; 16)(p12.31; q23.1)], had been previously shown to be associated with male fertility and embryo transit.Conclusion: OGM accurately detects chromosomal SVs, especially cryptic BRTs and CCRs. It is a useful complement to routine human genetic diagnostics, such as karyotyping, and detects cryptic BRTs and CCRs more accurately than routine genetic diagnostics.

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Section: Introductionmentioning

confidence: 99%

Analysis of chromosomal structural variations in patients with recurrent spontaneous abortion using optical genome mapping

Rao,

Zhang,

Zou

et al. 2023

Front. Genet.

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Molecular Approaches in Fetal Malformations, Dynamic Anomalies and Soft Markers: Diagnostic Rates and Challenges—Systematic Review of the Literature and Meta-Analysis

et al. 2022

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Fetal malformations occur in 2–3% of pregnancies. They require invasive procedures for cytogenetics and molecular testing. “Structural anomalies” include non-transient anatomic alterations. “Soft markers” are often transient minor ultrasound findings. Anomalies not fitting these definitions are categorized as “dynamic”. This meta-analysis aims to evaluate the diagnostic yield and the rates of variants of uncertain significance (VUSs) in fetuses undergoing molecular testing (chromosomal microarray (CMA), exome sequencing (ES), genome sequencing (WGS)) due to ultrasound findings. The CMA diagnostic yield was 2.15% in single soft markers (vs. 0.79% baseline risk), 3.44% in multiple soft markers, 3.66% in single structural anomalies and 8.57% in multiple structural anomalies. Rates for specific subcategories vary significantly. ES showed a diagnostic rate of 19.47%, reaching 27.47% in multiple structural anomalies. WGS data did not allow meta-analysis. In fetal structural anomalies, CMA is a first-tier test, but should be integrated with karyotype and parental segregations. In this class of fetuses, ES presents a very high incremental yield, with a significant VUSs burden, so we encourage its use in selected cases. Soft markers present heterogeneous CMA results from each other, some of them with risks comparable to structural anomalies, and would benefit from molecular analysis. The diagnostic rate of multiple soft markers poses a solid indication to CMA.

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Prenatal Diagnosis by Chromosome Microarray Analysis, An Indian Experience

Cited by 2 publications

References 23 publications

Analysis of chromosomal structural variations in patients with recurrent spontaneous abortion using optical genome mapping

Analysis of chromosomal structural variations in patients with recurrent spontaneous abortion using optical genome mapping

Molecular Approaches in Fetal Malformations, Dynamic Anomalies and Soft Markers: Diagnostic Rates and Challenges—Systematic Review of the Literature and Meta-Analysis

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