Clinical application of chromosomal microarray analysis for the prenatal diagnosis of chromosomal abnormalities and copy number variations in fetuses with congenital heart disease

Xia, Yu; Yang, Yongchao; Huang, Steve S.; Wu, Yueheng; Li, Ping; Zhuang, Jian

doi:10.1002/pd.5249

Cited by 28 publications

(20 citation statements)

References 32 publications

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“…Among the fetuses with sonographic structural malformations, those with multiple malformations showed the greatest rate of CNVs (31.8%, 7/22), followed by fetuses with central nervous system malformations (25%, 4/16), congenital anomalies of the kidney and urinary tract (18.0%, 7/39), and congenital heart malformations (8%, 10/125). These findings are slightly different from those of a previous study 13 , in which cardiovascular, central nervous, gastrointestinal, and musculoskeletal system malformations were mostly associated with pathogenic CNVs.…”

Section: Discussioncontrasting

confidence: 99%

Copy number variations in ultrasonically abnormal late pregnancy fetuses with normal karyotypes

Cai

Lin

et al. 2020

Sci Rep

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Many fetuses are found to have ultrasonic abnormalities in the late pregnancy. The association of fetal ultrasound abnormalities in late pregnancy with copy number variations (CNVs) is unclear. We attempted to explore the relationship between types of ultrasonically abnormal late pregnancy fetuses and CNVs. Fetuses (n = 713) with ultrasound-detected abnormalities in late pregnancy and normal karyotypes were analyzed. Of these, 237 showed fetal sonographic structural malformations and 476 showed fetal non-structural abnormalities. Single nucleotide polymorphism (SNP)-based chromosomal microarray (CMA) was performed on the Affymetrix CytoScan HD platform. Using the SNP array, abnormal CNVs were detected in 8.0% (57/713) of the cases, with pathogenic CNVs in 32 cases and variants of uncertain clinical significance (VUS) in 25 cases. The detection rate of abnormal CNVs in fetuses with sonographic structural malformations (12.7%, 30/237) was significantly higher (P = 0.001) than that in the fetuses with non-structural abnormalities (5.7%, 27/476). Overall, we observed that when fetal sonographic structural malformations or non-structural abnormalities occurred in the third trimester of pregnancy, the use of SNP analysis could improve the accuracy of prenatal diagnosis and reduce the rate of pregnancy termination.

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Section: Discussioncontrasting

confidence: 99%

Copy number variations in ultrasonically abnormal late pregnancy fetuses with normal karyotypes

Cai

Lin

et al. 2020

Sci Rep

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“…25,26 One recent fetal cohort reported a prevalence of 16% pathogenic CNVs. 27 This proportion, however, reflects a selected population, as they only included those referred for invasive genetic testing.…”

Section: Discussionmentioning

confidence: 99%

The prevalence of genetic diagnoses in fetuses with severe congenital heart defects

Nisselrooij

Lugthart

Clur

et al. 2020

Genetics in Medicine

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Purpose: Congenital heart defects (CHD) are associated with genetic syndromes. Rapid aneuploidy testing and chromosome microarray analysis (CMA) are standard care in fetal CHD. Many genetic syndromes remain undetected with these tests. This cohort study aims to estimate the frequency of causal genetic variants, in particular structural chromosome abnormalities and sequence variants, in fetuses with severe CHD at mid-gestation, to aid prenatal counselling. Methods: Fetuses with severe CHD were extracted from the PRECOR registry (2012-2016). We evaluated pre-and postnatal genetic testing results retrospectively to estimate the frequency of genetic diagnoses in general, as well as for specific CHDs. Results: 919 fetuses with severe CHD were identified. After exclusion of 211 cases with aneuploidy, a genetic diagnosis was found in 15.7% (111/708). These comprised copy number variants in 9.9% (70/708). In 4.5% (41/708) sequence variants were found that would have remained undetected with CMA. Interrupted aortic arch, pulmonary atresia with ventricular septal defect and atrioventricular septal defect were most commonly associated with a genetic diagnosis. Conclusion: In case of normal CMA results, parents should be offered exome sequencing sequentially, if time allows for it, especially if the CHD is accompanied by other structural malformations due to the large variety in genetic syndromes.

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“…Our data showed that the prevalence of abnormal CNVs was significantly higher in fetuses with cardiac and extracardiac malformations than in those with single or multiple cardiac malformations (P<0.05), and a high detection of abnormal CNVs was seen in fetuses with multiple cardiac malformations than in those with a single cardiac malformation (P<0.05), which was inconsistent with previous reports. [38][39][40] This may be because more fetuses with CHD were enrolled in our study, and the number of subjects was comparable among groups. Compared with previous studies, [38][39][40] this study is more persuasive, and our data demonstrate a strong correlation between fetal multiple malformations and abnormal CNVs.…”

Section: Discussionmentioning

confidence: 99%

“…[38][39][40] This may be because more fetuses with CHD were enrolled in our study, and the number of subjects was comparable among groups. Compared with previous studies, [38][39][40] this study is more persuasive, and our data demonstrate a strong correlation between fetal multiple malformations and abnormal CNVs.…”

Section: Discussionmentioning

confidence: 99%

SNP Array as a Tool for Prenatal Diagnosis of Congenital Heart Disease Screened by Echocardiography: Implications for Precision Assessment of Fetal Prognosis

Huang¹,

Cai²,

Wang³

et al. 2021

RMHP

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Objective This study aimed to examine the effectiveness of the SNP array for the prenatal diagnosis of congenital heart disease (CHD) screened by echocardiography. Patients and Methods A total of 356 pregnant women with fetal congenital heart malformations revealed by echocardiography at the Center for Prenatal Diagnosis of Fujian Maternal and Children Hospital during the period from November 2016 through July 2019 were recruited. The fetuses were assigned into three cohorts, including 142 with a single cardiac malformation, 106 with multiple cardiac malformations and 108 with cardiac and extracardiac malformations. All fetuses underwent chromosomal karyotyping and SNP array simultaneously, and the effectiveness of the SNP array for the prenatal diagnosis of CHD was evaluated. Results The overall prevalence of abnormal karyotypes was 9.3% among the 356 fetuses with CHD, and a higher proportion was found in fetuses with cardiac and extracardiac malformations (18.5%) than in those with single (5.6%) or multiple cardiac malformations (4.7%) ( P <0.05). Consistent with karyotype analysis, SNP array detected an additional 25 fetuses with pathogenic copy number variations (CNVs), seven with variant of unknown significance (VOUS) and seven with benign CNVs, and a lower proportion of abnormal CNV was found in fetuses with a single cardiac malformation (4.2%) than in those with multiple cardiac malformations (9.4%) or cardiac and extracardiac malformations (14.8%) ( P <0.05). Among the 33 fetuses with chromosomal abnormality, postnatal follow-up showed termination of pregnancy in 25 with pathogenic CNVs, one with VOUS, and six with normal karyotypes and SNP array findings but severe multiple malformations by ultrasonography. Conclusion SNP array increases the overall detection of abnormal CNVs by 9%, which improves the detection of CNVs associated with CHD. SNP array may serve as a tool for prenatal diagnosis of CHD that facilitates the discovery of pathogenic genes associated with CHD and provide valuable insights into the precision assessment of fetal prognosis during the prenatal counseling.

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Clinical application of chromosomal microarray analysis for the prenatal diagnosis of chromosomal abnormalities and copy number variations in fetuses with congenital heart disease

Abstract: This study shows that CMA is particularly effective for identifying chromosomal abnormalities and CNVs in fetuses with CHDs as well as having an effect on obstetrical outcomes. The elucidation of the genetic basis of CHDs will continue to expand our understanding of the etiology of CHDs.

Cited by 28 publications

References 32 publications

Copy number variations in ultrasonically abnormal late pregnancy fetuses with normal karyotypes

Copy number variations in ultrasonically abnormal late pregnancy fetuses with normal karyotypes

The prevalence of genetic diagnoses in fetuses with severe congenital heart defects

SNP Array as a Tool for Prenatal Diagnosis of Congenital Heart Disease Screened by Echocardiography: Implications for Precision Assessment of Fetal Prognosis

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