Prenatal Cytogenetic Results From Cases Referred for 44 Different Types of Abnormal Ultrasound Findings

Hanna, Julie Sanford; Neu, Richard L.; Lockwood, David H.

doi:10.1002/(sici)1097-0223(199602)16:2<109::aid-pd818>3.0.co;2-d

Cited by 23 publications

(4 citation statements)

References 8 publications

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“…When considering the ultrasound markers of chromosomal anomalies, the observed positive predictive values in our study are concordant with results obtained in other studies (Favre and Kohler, 1994;Pandya et al, 1994;Sanford et al, 1996;Stoll et al, 1992;Nicolaides et al, 1992a,b). Looking at the entire effectiveness of the ultrasound markers to detect a chromosomal anomaly, a stable rate of detected anomalies, from one to five per cent, was observed for each group of chromosomal aberrations, with a non-significant tendency to increase for trisomy 21.…”

Section: Discussionsupporting

confidence: 93%

Population screening for aneuploidy using maternal age and ultrasound

Cans

Amblard²,

Devillard³

et al. 1998

Prenat. Diagn.

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Section: Discussionsupporting

confidence: 93%

Population screening for aneuploidy using maternal age and ultrasound

Cans

Amblard²,

Devillard³

et al. 1998

Prenat. Diagn.

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“…That is, instead of performing two separate analyses to detect CNVs and SNVs, such as CMA followed by ES, WGS can offer both these analyses and, if needed, also targeted analyses for specific repeat expansions and uniparental disomy. Given that roughly 25% of fetal malformations are caused by chromosomal aberrations [3][4][5][6][7][8][9] , the diagnostic yield of WGS could approach 50% if fetuses with chromosomal aberrations are included.…”

Section: Discussionmentioning

confidence: 99%

“…When a malformation is detected, further investigation usually includes invasive testing with rapid aneuploidy detection, for example, with quantitative fluorescent polymerase chain reaction (QF-PCR), in order to identify the aneuploidy, and a subsequent chromosomal microarray analysis (CMA), which may detect smaller copy-number variants (CNVs). A conventional karyotype analysis will show an underlying genetic cause in approximately 14-18% of the cases [3][4][5][6] . CMA can contribute an additional 6-8% increase in the diagnostic yield 3,5,[7][8][9] .…”

Section: Introductionmentioning

confidence: 99%

Whole‐genome sequencing in prenatally detected congenital malformations: prospective cohort study in clinical setting

Westenius,

Conner,

Pettersson

et al. 2024

Ultrasound in Obstet & Gyne

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OBJECTIVESTo investigate the diagnostic yield of whole genome sequencing (WGS) in fetuses with various types of congenital malformations referred to a tertiary center for prenatal diagnosis.METHODSIn this prospective study, 50 fetuses with different congenital malformations, negative for trisomies and causative copy number variants, were further analyzed with fetal‐parental trio WGS analysis. Parents were eligible for inclusion if they accepted further investigation following the detection of isolated or multiple malformations during prenatal ultrasound. Cases with isolated increased nuchal translucency, gamete donation and multiple pregnancies were excluded. WGS with Illumina 30X PCR‐free short‐read sequencing included the analysis of single nucleotide variants, insertions and deletions, structural variants, short tandem repeats and copy number identification of SMN1 and SMN2 genes.RESULTSA molecular diagnosis was achieved in 13/50 (26%) of cases. Causative sequence variants were identified in 12 genes: FGFR3 (n=2), ACTA1 (n=1), CDH2 (n=1), COL1A2 (n=1), DHCR7 (n=1), EYA1 (n=1), FBXO11 (n=1), FRAS1 (n=1), L1CAM (n=1), OFD1 (n=1), PDHA1 (n=1) and SOX9 (n=1). The phenotypes of the cases were divided into different groups with following diagnostic yields: skeletal 4/9 (44%), multisystem 3/7 (43%), CNS 5/15 (33%) and thorax 1/10 (10%). Additionally, two cases carried variants that were considered potentially clinically relevant even if they were assessed as variants of uncertain significance according to the guidelines provided by the American College of Medical Genetics and Genomics. Overall, we identified a causative or potentially clinically relevant variant in 15/50 (30%) of cases.CONCLUSIONSWe demonstrate a diagnostic yield of 26% with clinical WGS in prenatally detected congenital malformations. Our study emphasizes the benefits that WGS can bring to the diagnosis of fetal structural anomalies. It is important to note that causative chromosome aberrations were excluded from our cohort before WGS. As chromosome aberrations are a well‐known cause of prenatally detected congenital malformations, future studies using WGS as a primary diagnostic test, including assessment of chromosome aberrations, will most likely show that the detection rate will exceed the diagnostic yield of this study. WGS can hereby add clinically relevant information, explaining the underlying cause of the fetal anomaly, which will provide information concerning the specific prognosis of the condition as well as estimate the risk of recurrence. A genetic diagnosis can also provide more reproductive choices in future pregnancies.This article is protected by copyright. All rights reserved.

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“…Fetal structural abnormalities are the main indications for invasive prenatal genetic testing, which is traditionally performed using karyotype analysis. The incidence of chromosomal abnormalities is approximately 5.4-15.5% when ultrasound identifies multiple system abnormalities in a fetus [10,11]. Further, chromosome microarray analysis (CMA) detection of fetuses with a negative karyotype results in an increase in the detection rate of genomic microdeletions and microduplications by 4-6% [12][13][14].…”

Section: And Turnermentioning

confidence: 99%

Chromosome Microarray Analysis and Exome Sequencing: Implementation in Prenatal Diagnosis of Fetuses with Digestive System Malformations

Wang,

Liu,

et al. 2023

Genes

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(1) Purpose: Retrospective back-to-back comparisons were performed to evaluate the accuracy, effectiveness, and incremental yield of chromosome microarray analysis (CMA) and exome sequencing (ES) analysis in fetuses with digestive system malformations (DSMs). (2) Methods: In total, 595 women with fetal DSMs who underwent prenatal diagnosis were enrolled. We analyzed the diagnostic yields of CMA and ES and evaluated pregnancy outcomes. Copy number variants (CNVs) were classified according to the American College of Medical Genetics and Genomics guidelines. (3) Results: Pathogenic CNVs were detected in 11/517 (2.12%) fetuses, and variants of unknown significance (VUS) were identified in 69 (13.35%) fetuses using CMA. ES detected 29 pathogenic/likely pathogenic variants in 23/143 (16.08%) fetuses and 26/143 (18.2%) VUS. In those with other ultrasound abnormalities, the detection rate of multiple system structural malformations was 41.2%, followed by skeletal (33.3%), cardiovascular (25.4%), and central nervous system (18.6%) malformations. Of the 391 surviving children, 40 (10.2%) exhibited varying degrees of mental retardation. (4) Conclusion: A correlation exists between DSMs and chromosomal abnormalities. When combined with other systemic abnormalities, the incidence of chromosomal abnormalities increases significantly. Patients with congenital DSM are at risk of developing neurodevelopmental disorders. Combined CMA and ES detection of fetal DSM has good clinical application potential.

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Prenatal Cytogenetic Results From Cases Referred for 44 Different Types of Abnormal Ultrasound Findings

Cited by 23 publications

References 8 publications

Population screening for aneuploidy using maternal age and ultrasound

Population screening for aneuploidy using maternal age and ultrasound

Whole‐genome sequencing in prenatally detected congenital malformations: prospective cohort study in clinical setting

Chromosome Microarray Analysis and Exome Sequencing: Implementation in Prenatal Diagnosis of Fetuses with Digestive System Malformations

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