Comprehensive evaluation of genetic variants using chromosomal microarray analysis and exome sequencing in fetuses with congenital heart defect

Qiao, Fengxiang; Wang, Yishuang; Zhang, C.; Zhou, Ran; Wu, Yifei; Wang, C.; Meng, Lü; Mao, Ping; Cheng, Qi; Luo, Chen; Hu, Ping; Xu, Zhengfeng

doi:10.1002/uog.23532

Cited by 36 publications

(35 citation statements)

References 46 publications

(132 reference statements)

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“…Overall, the yield of the CMA test in our study was consistent with that of previously published data. However, the detection rate of our pathogenic sequence variants was higher than that reported in existing literature [24][25][26]. We suggest CMA as a first-tier test in foetuses with CHD, and that WES can be offered sequentially if CMA results are negative.…”

Section: Discussioncontrasting

confidence: 56%

Estimating the frequency of causal genetic variants in foetuses with congenital heart defects: a Chinese cohort study

Xue

Zhang

et al. 2022

Orphanet J Rare Dis

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Background The belief that genetics plays a major role in the pathogenesis of congenital heart defects (CHD) has grown popular among clinicians. Although some studies have focused on the genetic testing of foetuses with CHD in China, the genotype–phenotype relationship has not yet been fully established, and hotspot copy number variations (CNVs) related to CHD in the Chinese population are still unclear. This cohort study aimed to assess the prevalence of chromosomal abnormalities in Chinese foetuses with different types of CHD. Results In a cohort of 200 foetuses, chromosomal abnormalities were detected in 49 (24.5%) after a prenatal chromosome microarray analysis (CMA), including 23 foetuses (11.5%) with aneuploidies and 26 (13.0%) with clinically significant CNVs. The additional diagnostic yield following whole exome sequencing (WES) was 11.5% (6/52). The incidence of total chromosomal abnormality in the non-isolated CHD group (31.8%) was higher than that in the isolated CHD group (20.9%), mainly because the incidence of aneuploidy was significantly increased when CHD was combined with extracardiac structural abnormalities or soft markers. The chromosomal abnormality rate of the complex CHD group was higher than that of the simple CHD group; however, the difference was not statistically significant (31.8% vs. 23.6%, P = 0.398). The most common CNV detected in CHD foetuses was the 22q11.2 deletion, followed by deletions of 5p15.33p15.31, deletions of 15q13.2q13.3, deletions of 11q24.2q25, deletions of 17p13.3p13.2, and duplications of 17q12. Conclusions CMA is the recommended initial examination for cases of CHD in prenatal settings, for both simple heart defects and isolated heart defects. For cases with negative CMA results, the follow-up application of WES will offer a considerable proportion of additional detection of clinical significance.

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Section: Discussioncontrasting

confidence: 56%

Estimating the frequency of causal genetic variants in foetuses with congenital heart defects: a Chinese cohort study

Xue

Zhang

et al. 2022

Orphanet J Rare Dis

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“…Recent studies have shown that exome sequencing increased the prenatal detection rate of pathogenic variants of CHD by 5.8%-6.7%. 25,34 The increased detection rate of exome sequencing in prenatal diagnosis of CHD might identify the causes of CHD in addition to chromosomal disorders, thus providing parents with more options regarding continuing pregnancy and further reducing the postnatal mortality of fetuses with CHD. However, more prospective studies are warranted.…”

Section: Limitationsmentioning

confidence: 99%

Pregnancy outcomes of fetuses with congenital heart disease after a prenatal diagnosis with chromosome microarray

Zhang

Wang

et al. 2021

Prenatal Diagnosis

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Objective: To evaluate the pregnancy outcomes of fetuses with congenital heart disease (CHD) after chromosome microarray (CMA)-based prenatal diagnosis.Method: Amniocentesis was performed in 1035 pregnant women carrying fetuses with CHD between September 2014 and December 2019. Chromosomal aberrations in fetuses with CHD were evaluated using CMA. The pregnancy outcomes were followed up from 6 months to 5 years. Results:The overall CHD detection rate by CMA was 10.1% (105/1035; 50 fetuses: aneuploidy, 55 fetuses: pathogenic or likely pathogenic copy number variations).Among 1003 fetuses who were followed up, 4, 236, 763, and 18 cases were of miscarriages, pregnancy termination, live births, and postnatal deaths, respectively. Self-healed CHD was observed in 401 (52.6%) fetuses. The pregnancy termination rate of fetuses with chromosomal anomalies was significantly higher than that of fetuses without chromosomal anomalies (93.1% vs. 15.5%, p < 0.001). However, other pregnancy outcomes, including mortality, preterm labor, and low-weight birth rate, were similar between the two groups. Conclusion:The outcome of CMA is an important factor influencing parents' choice of whether to continue the pregnancy. Self-healing rate of prenatal diagnosed CHD is high. The mortality and morbidity of fetuses with CHD following prenatal CMA testing are relatively low. Key pointsWhat's already known about this topic?� Chromosomal microarray analysis (CMA) is a reliable and high-resolution technology and should be used as a first-tier test for the prenatal diagnosis of congenital heart disease (CHD) in clinical practice. What does this study add?� The mortality and morbidity of fetuses with CHD following prenatal CMA testing are relatively low.� Self-healing rate of prenatally diagnosed CHD, especially minor CHD, is high.

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“…Although aneuploidies were more frequent in fetuses with nonisolated CHDs, the frequency of copy number variants and sequence variants was not significantly different among fetuses with isolated vs. nonisolated CHDs. The authors of this study conclude that ES should be offered prenatally in all cases of CHDs with normal CMA results (Qiao et al., 2020).…”

Section: Considerations For Prenatal Genetic Counselingmentioning

confidence: 89%

“…Studies of ES in the prenatal setting are emerging (Lord et al,2019;Petrovski et al,l., 2019;Westphal et al, 2019) (Qiao et al, 2020).…”

mentioning

confidence: 99%

Genetic counseling for congenital heart disease – Practice resource of the National Society of Genetic Counselors

Ison

Griffin

Parrott

et al. 2021

Journal of Genetic Counseling

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Congenital heart disease (CHD) is an indication which spans multiple specialties across various genetic counseling practices. This practice resource aims to provide guidance on key considerations when approaching counseling for this particular indication while recognizing the rapidly changing landscape of knowledge within this domain. This resource was developed with consensus from a diverse group of certified genetic counselors utilizing literature relevant for CHD genetic counseling practice and is aimed at supporting genetic counselors who encounter this indication in their practice both pre-and postnatally.

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Comprehensive evaluation of genetic variants using chromosomal microarray analysis and exome sequencing in fetuses with congenital heart defect

Cited by 36 publications

References 46 publications

Estimating the frequency of causal genetic variants in foetuses with congenital heart defects: a Chinese cohort study

Estimating the frequency of causal genetic variants in foetuses with congenital heart defects: a Chinese cohort study

Pregnancy outcomes of fetuses with congenital heart disease after a prenatal diagnosis with chromosome microarray

Genetic counseling for congenital heart disease – Practice resource of the National Society of Genetic Counselors

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