Prenatal diagnosis of chromosomal mosaicism in over 1600 cases using array comparative genomic hybridization as a first line test

Carey, Louise; Scott, Fergus; Murphy, Kristi; Mansfield, Nerida; Barahona, Paulette; Leigh, Don; Robertson, Rob; McLennan, Andrew

doi:10.1002/pd.4332

Cited by 27 publications

(31 citation statements)

References 39 publications

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“…Confined placental mosaicism detected at prenatal diagnosis using CVS is a well‐documented phenomenon. Chromosome analysis by traditional karyotyping is reported to have mosaicism detected in 1% to 2% of first trimester pregnancies, and the detection rate using microarray is quite comparable . Similarly, in this study, we observed mosaicism in 3.0% (42 out of 1382) of the CVS cases using CMA.…”

Section: Discussioncontrasting

confidence: 82%

“…Chromosomal microarray analysis significantly increases the diagnostic yield compared with conventional karyotyping yet without significantly increasing the frequency of detecting variants of unknown significance . In addition, it has been demonstrated to be a powerful tool to detect mosaicism at levels as low as 9% . However, while cytogenetic analysis of the cytotrophoblast layer of CVS tissue is no longer conducted in many laboratories, primarily because of the labor‐intensive procedure of requiring both short‐ and long‐term cultures, microarrays are frequently performed on intact CVS tissue that includes this outer cell layer.…”

Section: Introductionmentioning

confidence: 99%

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Chromosomal microarray analysis on uncultured chorionic villus sampling can be complicated by confined placental mosaicism for aneuploidy and microdeletions

Jernegan

Veyver

et al. 2018

Prenatal Diagnosis

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Section: Discussioncontrasting

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Chromosomal microarray analysis on uncultured chorionic villus sampling can be complicated by confined placental mosaicism for aneuploidy and microdeletions

Jernegan

Veyver

et al. 2018

Prenatal Diagnosis

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“…Based on our results, and in agreement with recently published data [45,46], we can conclude that aCGH performed on directly extracted DNA is in fact equally suited, if not superior, to routine karyotype for the detection of low level mosaic aneuploidy, bearing in mind that classic karyotype analysis must examine at least 20 metaphases in order to reliably detect the presence of mosaicism at a level of ≥15%, which is not routine practice in PCD (typically 16 metaphases are counted).…”

Section: Resultssupporting

confidence: 83%

Dilemmas in Prenatal Chromosomal Diagnosis Revealed Through a Single Center's 30 Years' Experience and 90,000 Cases

2015

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Introduction: The aim of this article is to provide a perspective of prenatal chromosomal diagnosis (PCD) derived from a single center's evolving experience from ∼90,000 consecutive prenatal cases and to highlight important issues and current dilemmas. Materials and Methods: Prenatal cases in this study (1985-2013) were referred for various indications, and PCD was performed by standard karyotype in 84,255 cases, multiplex ligation-dependent probe amplification (MLPA) panel in 3,010 cases and standalone array comparative genomic hybridization (aCGH) in 3,122 cases. Results: Classic karyotype revealed 1.7 and 7.9% of pathological cases in amniotic fluid and CVS samples, respectively, with common aneuploidies accounting for 59.6 and 64.3% of the total abnormal. Molecular approaches increased the diagnostic yield by 0.6% for MLPA and 1.6% for aCGH, uncovering pathogenic chromosomal abnormalities undetectable by karyotype analysis. Conclusions: Current molecular diagnostic capabilities and the recent introduction of noninvasive prenatal testing (NIPT) point to one current major dilemma in PCD, with serious implications in genetic counseling, relating on the one hand to reaping the benefits from the high detection rate afforded through aCGH but accepting an invasive risk, and on the other hand, offering a lower detection rate practically only for Down syndrome, with minimal invasive risk.

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“…It was once reported as 65% and 70% during the early mitotic stage [41, 42], and as 10% during the blastocyst stage [4]. The chromosomal mosaicism was also observed in the prenatal tests of non-IVF people, including chorionic villus (about 1.78%) and amniotic fluid (about 0.46%) [43]. The propagation of abnormal cell line(s) in the mosaic embryos had negative effect in the pregnancy, and the undetected mosaicism and aneuploidies in the PGS/aCGH was recently reported as a cause to the first trimester pregnancy loss [44].…”

Section: Discussionmentioning

confidence: 99%

Identification of mosaic and segmental aneuploidies by next-generation sequencing in preimplantation genetic screening can improve clinical outcomes compared to array-comparative genomic hybridization

Lai¹,

Chuang²,

Wong³

et al. 2017

Mol Cytogenet

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BackgroundChromosomal mosaicism is observed as the presence of both euploid and aneuploid cells in a particular blastocyst. Recent studies have reported that the implantation rate of mosaic embryo transfer is remarkably lower than the euploid embryos. The superior capability of next-generation sequencing (NGS) to detect chromosomal mosaicism in preimplantation genetic screening (PGS) remains controversial, and several data displayed similar implantation and pregnancy rates using NGS or array comparative genomic hybridization (aCGH).ResultsIn this study, the main inconsistency of aneuploidy detection and clinical performance between the NGS and aCGH were assessed. The phase I consisted of a parallel comparison in 182 blastocysts from 45 selected PGS patients for both the NGS and aCGH platforms. The phase II retrospectively compared the clinical outcomes of 90 patients with NGS-screened euploid embryo transfer to that of 129 patients with aCGH-screened euploid embryo transfer. The parallel comparison showed that the inconsistency of embryo euploidy was 11.8% (p = 0.01). Chromosomal mosaicism (10.7% with NGS vs. 3.9% with aCGH) and segmental aneuploidy (10.7% with NGS vs. 6.7% with aCGH) contributed to the discrepancy mainly. The chromosomally mosaic embryos (20%–50% of aneuploidy) and several embryos with segmental aneuploidy (≥10 Mbp) were hard to distinguish using the aCGH platform, but could be clearly identified using the NGS platform. After the first euploid embryo cryotransfer, the β-HCG(+) rate and implantation rate significantly increased in the PGS/NGS patients (HCG[+] rate: 73.3% in PGS/NGS vs. 60.5% in PGS/aCGH, p = 0.048; implantation rate: 53.2% in PGS/NGS vs. 45.0% in PGS/aCGH, p = 0.043). The clinical and ongoing pregnancy rates appeared higher in the NGS group, but did not reached statistical significance.ConclusionsThe results demonstrated that the NGS platform can identify embryos with chromosomal mosaicism and segmental aneuploidy more precisely than the aCGH platform, and the following clinical performance of NGS was more favorable.

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Prenatal diagnosis of chromosomal mosaicism in over 1600 cases using array comparative genomic hybridization as a first line test

Cited by 27 publications

References 39 publications

Chromosomal microarray analysis on uncultured chorionic villus sampling can be complicated by confined placental mosaicism for aneuploidy and microdeletions

Chromosomal microarray analysis on uncultured chorionic villus sampling can be complicated by confined placental mosaicism for aneuploidy and microdeletions

Dilemmas in Prenatal Chromosomal Diagnosis Revealed Through a Single Center's 30 Years' Experience and 90,000 Cases

Identification of mosaic and segmental aneuploidies by next-generation sequencing in preimplantation genetic screening can improve clinical outcomes compared to array-comparative genomic hybridization

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