Prenatal genetic diagnosis of omphalocele by karyotyping, chromosomal microarray analysis and exome sequencing.
Ontology highlight
ABSTRACT: Objectives
The aim of this study is to share our experience in the prenatal diagnosis of omphalocele by karyotyping, chromosomal microarray analysis (CMA) and whole exome sequencing (WES).Methods
In this retrospective study, 81 cases of omphalocele were identified from 2015 to 2020. Associated anomalies and prenatal diagnosis based on karyotyping, CMA and WES were analysed.Results
Fifty-eight (71.6%) of the 81 foetuses had other ultrasound anomalies. Giant omphalocele was present in 11 cases (13.6%) and small omphalocele was present in 70 cases (86.4%). Chromosomal abnormalities were found in 24 foetuses (29.6%, 24/81), the most common of which were trisomy 18 (58.8%, 11/24) and trisomy 13 (29.2%, 7/24). Compared to isolated omphalocele, non-isolated omphalocele was accompanied by an increased prevalence of chromosomal abnormalities (4.3% (1/23) vs. 39.7% (23/58), χ2 = 8.226, p = .004). All chromosomal abnormalities were found in small omphalocele. Aside from aneuploidy, CMA showed one pathogenic copy number variants (CNVs) for a detection rate of 1.2%, one variants of unknown significance (VOUS) and one instance of loss of heterozygosity (LOH). WES was performed on 3 non-isolated cases, and one was found to have pathogenic variants.Conclusions
The most common genetic cause of omphalocele is aneuploidy and the prevalence of chromosomal abnormalities is increased with non-isolated and small omphalocele. CMA and WES can be useful for providing further genetic information to assist in prenatal counselling and pregnancy management.
SUBMITTER: Shi X
PROVIDER: S-EPMC8366676 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundChromosomal microarray analysis has emerged as a primary diagnostic tool for the evaluation of developmental delay and structural malformations in children. We aimed to evaluate the accuracy, efficacy, and incremental yield of chromosomal microarray analysis as compared with karyotyping for routine prenatal diagnosis.MethodsSamples from women undergoing prenatal diagnosis at 29 centers were sent to a central karyotyping laboratory. Each sample was split in two; standard karyotyping was performed on one portion and the other was sent to one of four laboratories for chromosomal microarray.ResultsWe enrolled a total of 4406 women. Indications for prenatal diagnosis were advanced maternal age (46.6%), abnormal result on Down's syndrome screening (18.8%), structural anomalies on ultrasonography (25.2%), and other indications (9.4%). In 4340 (98.8%) of the fetal samples, microarray analysis was successful; 87.9% of samples could be used without tissue culture. Microarray analysis of the 4282 nonmosaic samples identified all the aneuploidies and unbalanced rearrangements identified on karyotyping but did not identify balanced translocations and fetal triploidy. In samples with a normal karyotype, microarray analysis revealed clinically relevant deletions or duplications in 6.0% with a structural anomaly and in 1.7% of those whose indications were advanced maternal age or positive screening results.ConclusionsIn the context of prenatal diagnostic testing, chromosomal microarray analysis identified additional, clinically significant cytogenetic information as compared with karyotyping and was equally efficacious in identifying aneuploidies and unbalanced rearrangements but did not identify balanced translocations and triploidies. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; ClinicalTrials.gov number, NCT01279733.).
| S-EPMC3549418 | biostudies-literature
Project description:To investigate the incidence and clinical significance of chromosomal mosaicism (CM) in prenatal diagnosis by G-banding karyotyping and chromosomal microarray analysis (CMA). This is a single-centre retrospective study of invasive prenatal diagnosis for CM. From 5758 karyotyping results and 6066 CMA results, 104 foetal cases with CM were selected and analysed further. In total, 50% (52/104) of foetal cases with CM were affected by ultrasound-detectable phenotypes. Regardless of whether they were singleton or twin pregnancies, isolated structural defects in one system (51.35%, 19/37 in singletons; 86.67%, 13/15 in twins) and a single soft marker (18.92%, 7/37 in singletons; 13.33%, 2/15 in twins) were the most common ultrasound anomalies. Mosaic autosomal trisomy (19.23%, 20/104) was the most frequent type, and its rate was higher in phenotypic foetuses (28.85%, 15/52) than in non-phenotypic foetuses (9.62%, 5/52). There was no difference in mosaic fractions between phenotypic and non-phenotypic foetuses based on specimen sources or overall classification. Discordant mosaic results were observed in 16 cases (15.38%, 16/104) from different specimens or different testing methods. Genetic counselling and clinical management regarding CM in prenatal diagnosis remain challenging due to the variable phenotypes and unclear significance. Greater caution should be used in prenatal counselling, and more comprehensive assays involving serial ultrasound examinations, different specimens or testing methods verifications and follow-up should be applied.
| S-EPMC7810963 | biostudies-literature
Project description:Objective: In the study, we investigated the genetic etiology of the ventricular septal defect (VSD) and comprehensively evaluated the diagnosis rate of prenatal chromosomal microarray analysis (CMA) and exome sequencing (ES) for VSD to provide evidence for genetic counseling. Methods: We carried out chromosomal microarray analysis (CMA) on 468 fetuses with VSD and exome sequencing (ES) on 51 fetuses. Results: In our cohort, 68 (14.5%) VSD fetuses received a genetic diagnosis, including 61 (13.03%, 61/468) cases with chromosomal abnormalities and seven (13.7%, 7/51) cases with gene sequence variants. The detection rate of total pathogenic and likely pathogenic gene variations in the non-isolated VSD group (61/335, 18.2%, 55 by QF-PCR/karyotype/CMA + 6 by ES) was significantly higher than that in the isolated VSD group (7/133, 5.3%, 6 by QF-PCR/karyotype/CMA + 1 by ES, p = 0.000). The most common copy number variation (CNV) was 22q11.2 microdeletion syndrome. Additionally, we found six previously unreported variants, which expanded the variation spectrum of VSD-related genes. Conclusion: In this study, CNVs and sequence variants were found in 13.03% and 13.7% of cases, respectively. ES can be recommended for fetuses with VSD without chromosome abnormalities and pathogenic CNVs, especially those that are combined with other ultrasound abnormalities.
| S-EPMC10704506 | biostudies-literature
Project description:Chromosomal microarray analysis (CMA) is performed either by array comparative genomic hybridization or by using a single nucleotide polymorphism array. In the prenatal setting, CMA is on par with traditional karyotyping for detection of major chromosomal imbalances such as aneuploidy and unbalanced rearrangements. CMA offers additional diagnostic benefits by revealing sub-microscopic imbalances or copy number variations that are too small to be seen on a standard G-banded chromosome preparation. These submicroscopic imbalances are also referred to as microdeletions and microduplications, particularly when they include specific genomic regions that are associated with clinical sequelae. Not all microdeletions/duplications are associated with adverse clinical phenotypes and in many cases, their presence is benign. In other cases, they are associated with a spectrum of clinical phenotypes that may range from benign to severe, while in some situations, the clinical significance may simply be unknown. These scenarios present a challenge for prenatal diagnosis, and genetic counseling prior to prenatal CMA greatly facilitates delivery of complex results. In prenatal diagnostic samples with a normal karyotype, chromosomal microarray will diagnose a clinically significant subchromosomal deletion or duplication in approximately 1% of structurally normal pregnancies and 6% with a structural anomaly. Pre-test counseling is also necessary to distinguish the primary differences between the benefits, limitations and diagnostic scope of CMA versus the powerful but limited screening nature of non-invasive prenatal diagnosis using cell-free fetal DNA.
| S-EPMC5856154 | biostudies-literature
Project description:PurposeEmerging studies suggest that low-pass genome sequencing (GS) provides additional diagnostic yield of clinically significant copy-number variants (CNVs) compared with chromosomal microarray analysis (CMA). However, a prospective back-to-back comparison evaluating accuracy, efficacy, and incremental yield of low-pass GS compared with CMA is warranted.MethodsA total of 1023 women undergoing prenatal diagnosis were enrolled. Each sample was subjected to low-pass GS and CMA for CNV analysis in parallel. CNVs were classified according to guidelines of the American College of Medical Genetics and Genomics.ResultsLow-pass GS not only identified all 124 numerical disorders or pathogenic or likely pathogenic (P/LP) CNVs detected by CMA in 121 cases (11.8%, 121/1023), but also defined 17 additional and clinically relevant P/LP CNVs in 17 cases (1.7%, 17/1023). In addition, low-pass GS significantly reduced the technical repeat rate from 4.6% (47/1023) for CMA to 0.5% (5/1023) and required less DNA (50 ng) as input.ConclusionIn the context of prenatal diagnosis, low-pass GS identified additional and clinically significant information with enhanced resolution and increased sensitivity of detecting mosaicism as compared with the CMA platform used. This study provides strong evidence for applying low-pass GS as an alternative prenatal diagnostic test.
| S-EPMC7042067 | biostudies-literature
Project description:Novel methodologies for detection of chromosomal abnormalities have been made available in the recent years but their clinical utility in prenatal settings is still unknown. We have conducted a comparative study of currently available methodologies for detection of chromosomal abnormalities after invasive prenatal sampling.A multicentric collection of a 1-year series of fetal samples with indication for prenatal invasive sampling was simultaneously evaluated using three screening methodologies: (1) karyotype and quantitative fluorescent polymerase chain reaction (QF-PCR), (2) two panels of multiplex ligation-dependent probe amplification (MLPA), and (3) chromosomal microarray-based analysis (CMA) with a targeted BAC microarray. A total of 900 pregnant women provided informed consent to participate (94% acceptance rate). Technical performance was excellent for karyotype, QF-PCR, and CMA (~1% failure rate), but relatively poor for MLPA (10% failure). Mean turn-around time (TAT) was 7 days for CMA or MLPA, 25 for karyotype, and two for QF-PCR, with similar combined costs for the different approaches. A total of 57 clinically significant chromosomal aberrations were found (6.3%), with CMA yielding the highest detection rate (32% above other methods). The identification of variants of uncertain clinical significance by CMA (17, 1.9%) tripled that of karyotype and MLPA, but most alterations could be classified as likely benign after proving they all were inherited. High acceptability, significantly higher detection rate and lower TAT, could justify the higher cost of CMA and favor targeted CMA as the best method for detection of chromosomal abnormalities in at-risk pregnancies after invasive prenatal sampling.
| S-EPMC3277707 | biostudies-literature
Project description:Background: To assess the value of chromosomal microarray analysis (CMA) during the prenatal diagnosis of high-risk pregnancies. Methods: Between January 2016 and November 2021, we included 178 chorionic villi and 859 amniocentesis samples from consecutive cases at a multiple tertiary hospital. Each of these high-risk singleton pregnancies had at least one of the following indications: (1) advanced maternal age (AMA; ≥35 years; 546, 52.7%); (2) fetal structural abnormality on ultrasound (197, 19.0%); (3) high-risk first- or second-trimester Down syndrome screen (189, 18.2%), including increased nuchal translucency (≥3.5 mm; 90, 8.7%); or (4) previous pregnancy, child, or family history (105, 10.1%) affected by chromosomal abnormality or genetic disorder. Both G-banding karyotype analysis and CMA were performed. DNA was extracted directly and examined with oligonucleotide array-based comparative genomic hybridization. Results: Aneuploidies were detected by both G-banding karyotyping and CMA in 42/1037 (4.05%) cases. Among the 979 cases with normal karyotypes, 110 (10.6%) cases had copy number variants (CNVs) in CMA, including 30 (2.9%) cases with reported pathogenic and likely pathogenic CNVs ≥ 400 kb, 37 (3.6%) with nonreported VOUS, benign, or likely benign CNVs ≥ 400 kb, and 43 (4.1%) with nonreported CNVs < 400 kb. Of the 58 (5.6%) cases with aneuploidy rearrangements, 42 (4.1%) were diagnosed by both G-banding karyotyping and CMA; four inversions, six balanced translocations, and six low mosaic rates were not detected with CMA. Conclusions: CMA is an effective first step for the prenatal diagnosis of high-risk pregnancies with fetal structural anomalies found in ultrasonography or upon positive findings.
| S-EPMC9267905 | biostudies-literature
Project description:Ventriculomegaly is considered to be linked to abnormal neurodevelopment outcome. The aim of this retrospective study was to investigate the current applications of chromosomal microarray analysis (CMA) in foetuses with ventriculomegaly. A total of 548 foetuses with ventriculomegaly detected by prenatal ultrasound underwent single nucleotide polymorphism (SNP) array testing and were subjected to long-term follow-up. The overall prevalence of chromosomal aberrations was 7.30% (40/548), including 4.20% (23/548) with pathogenic/likely pathogenic copy number variants. The incidence of chromosomal aberrations was significantly higher in foetuses with bilateral ventriculomegaly than in those with unilateral ventriculomegaly (10.56% vs. 5.71%, P = 0.040), in foetuses with non-isolated ventriculomegaly than in those with isolated ventriculomegaly (12.99% vs. 2.38%, P < 0.0001), and in foetuses with severe ventriculomegaly than in those with mild-to-moderate ventriculomegaly (23.08% vs. 6.51%, P = 0.005). The outcome in foetuses with mild ventriculomegaly was significantly better than in those with moderate ventriculomegaly (95.60% vs. 84.00%, P = 0.003). Thus, CMA should be regarded as the first-tier test for prenatal diagnosis of foetal ventriculomegaly, especially in foetuses with bilateral or non-isolated ventriculomegaly. The outcome of foetuses with mild ventriculomegaly is favourable; however, there is an increased risk of neurodevelopmental disabilities in foetuses with moderate ventriculomegaly.
| S-EPMC7699619 | biostudies-literature
Project description:BackgroundChromosomal abnormalities are important causes of ventriculomegaly (VM). In mild and isolated cases of fetal VM, obstetricians rarely give clear indications for pregnancy termination. We aimed to calculate the incidence of chromosomal abnormalities and incremental yield of chromosomal microarray analysis (CMA) in VM, providing more information on genetic counseling and prognostic evaluation for fetuses with VM.MethodsThe Chinese language databases Wanfang Data, China National Knowledge Infrastructure, and China Biomedical Literature Database (from January 1, 1991 to April 29, 2020) and English language databases PubMed, Embase, and Cochrane Library (from January 1, 1945 to April 29, 2020) were systematically searched for articles on fetal VM. Diagnostic criteria were based on ultrasonographic or magnetic resonance imaging (MRI) assessment of lateral ventricular atrium width: ≥10 to <15 mm for mild VM, and ≥15 mm for severe VM. Isolated VM was defined by the absence of structural abnormalities other than VM detected by ultrasonography or MRI. R software was used for the meta-analysis to determine the incidence of chromosomal abnormalities and incremental yield of CMA in VM, and the combined rate and 95% confidence interval (CI) were calculated.ResultsTwenty-three articles involving 1635 patients were included. The incidence of chromosomal abnormalities in VM was 9% (95% CI: 5%-12%) and incremental yield of CMA in VM was 11% (95% CI: 7%-16%). The incidences of chromosomal abnormalities in mild, severe, isolated, and non-isolated VM were 9% (95% CI: 4%-16%), 5% (95% CI: 1%-11%), 3% (95% CI: 1%-6%), and 13% (95% CI: 4%-25%), respectively.ConclusionsApplying CMA in VM improved the detection rate of abnormalities. When VM is confirmed by ultrasound or MRI, obstetricians should recommend fetal karyotype analysis to exclude chromosomal abnormalities. Moreover, CMA should be recommended preferentially in pregnant women with fetal VM who are undergoing invasive prenatal diagnosis. CMA cannot completely replace chromosome karyotype analysis.
| S-EPMC8812611 | biostudies-literature
Project description:BackgroundThere are a few literature reports of prenatal ultrasound manifestations of Williams-Beuren syndrome. We aimed to explore the prenatal diagnosis of Williams-Beuren syndrome by ultrasound and chromosomal microarray analysis and describe the prenatal ultrasound performance of this syndrome.MethodsIn this retrospective study, we reported eight cases of Williams-Beuren syndrome diagnosed at our prenatal diagnostic center from 2016 to 2021. We systematically reviewed clinical data from these cases, including indications for invasive testing, sonographic findings, QF-PCR results, chromosomal microarray analysis results, and pregnancy outcomes.ResultsIn this study, the common ultrasound features were ventricular septal defect (37.5%), intrauterine growth retardation (25%), and aortic coarctation (25%). Moreover, all patients were found to have a common deletion in the Williams-Beuren syndrome chromosome region at the 7q11.23 locus, which contained the elastin gene. Deletion sizes ranged from 1.42 to 2.07 Mb. Seven parents asked for termination of pregnancy, and one patient was lost to follow-up.ConclusionsThis study is the most extensive prenatal study using chromosomal microarray analysis technology for detailed molecular analysis of Williams-Beuren syndrome cases. We reported three cases combined with first-reported ultrasound manifestations. Case 1 was concomitant with multicystic dysplastic kidney and duodenal atresia combined with case 3. Notably, case 4 was combined with multiple cardiovascular malformations: Tetralogy of Fallot, right aortic arch, and supravalvar aortic stenosis. These manifestations expand the intrauterine ultrasound phenotype of Williams-Beuren syndrome in previous literature reports.
| S-EPMC9238061 | biostudies-literature