Genomic imbalances in syndromic congenital heart disease

Molck, Miriam Coelho; Simioni, Milena; Vieira, Társis Paiva; Sgardioli, Ilária Cristina; Monteiro, Fabíola Paoli; Souza, Josiane; Fett‐Conte, Agnes Cristina; Félix, Têmis Maria; Monlleó, Isabella Lopes; Gil‐da‐Silva‐Lopes, Vera Lúcia

doi:10.1016/j.jped.2016.11.007

Cited by 30 publications

(20 citation statements)

References 28 publications

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“…Eugen-Matthias Strehle et al [ 55 ] studied 20 patients with 4q deletions and found significant genotype-phenotype correlations at a single gene level, linking specific phenotypes to individual genes. The authors reported an imbalance slightly smaller than ours and proposed a potentially critical region for 4q35 associated to CHD compromising the SORBS2 gene (616349) [ 56 ]. In addition, the patient from our cohort disclosed also a duplication on the CES region.…”

Section: Discussionmentioning

confidence: 84%

Genetic Imbalances in Argentinean Patients with Congenital Conotruncal Heart Defects

Delea

Espeche

Bruque

et al. 2018

Genes

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Congenital conotruncal heart defects (CCHD) are a subset of serious congenital heart defects (CHD) of the cardiac outflow tracts or great arteries. Its frequency is estimated in 1/1000 live births, accounting for approximately 10–30% of all CHD cases. Chromosomal abnormalities and copy number variants (CNVs) contribute to the disease risk in patients with syndromic and/or non-syndromic forms. Although largely studied in several populations, their frequencies are barely reported for Latin American countries. The aim of this study was to analyze chromosomal abnormalities, 22q11 deletions, and other genomic imbalances in a group of Argentinean patients with CCHD of unknown etiology. A cohort of 219 patients with isolated CCHD or associated with other major anomalies were referred from different provinces of Argentina. Cytogenetic studies, Multiplex-Ligation-Probe-Amplification (MLPA) and fluorescent in situ hybridization (FISH) analysis were performed. No cytogenetic abnormalities were found. 22q11 deletion was found in 23.5% of the patients from our cohort, 66% only had CHD with no other major anomalies. None of the patients with transposition of the great vessels (TGV) carried the 22q11 deletion. Other 4 clinically relevant CNVs were also observed: a distal low copy repeat (LCR)D-E 22q11 duplication, and 17p13.3, 4q35 and TBX1 deletions. In summary, 25.8% of CCHD patients presented imbalances associated with the disease.

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Section: Discussionmentioning

confidence: 84%

Genetic Imbalances in Argentinean Patients with Congenital Conotruncal Heart Defects

Delea

Espeche

Bruque

et al. 2018

Genes

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“…Due to the large sample size and completeness of our regional CHD registry, we were able to stratify the probability of genetic diagnoses according to the specific heart defect, using not only results from karyotyping and FISH for 22q11.2, but CMA, genetic testing for specific syndromes and exome sequencing in selected cases as well. Although several recent cohorts have studied aneuploidy or 22q11.2 deletion syndrome in CHD cases, 22,23,26,29 evidence on the prevalence of other structural chromosome abnormalities and sequence variants for specific heart defects is limited. IAoA, PA-VSD and AVSD were most associated with the presence of genetic diagnoses.…”

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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“…Congenital heart disease (CHD) is a common malformation affecting approximately six per 1000 live births, occurring as an isolated trait or related to multiple congenital anomalies [ 1 ]. Despite anatomical evaluation has a great contribution to the diagnosis and treatments of CHD, the hemodynamic evaluation is also indispensable.…”

Section: Introductionmentioning

confidence: 99%

Clinical validation and assessment of aortic hemodynamics using computational fluid dynamics simulations from computed tomography angiography

et al. 2018

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BackgroundHemodynamic information including peak systolic pressure (PSP) and peak systolic velocity (PSV) carry an important role in evaluation and diagnosis of congenital heart disease (CHD). Since MDCTA cannot evaluate hemodynamic information directly, the aim of this study is to provide a noninvasive method based on a computational fluid dynamics (CFD) model, derived from multi-detector computed tomography angiography (MDCTA) raw data, to analyze the aortic hemodynamics in infants with CHD, and validate these results against echocardiography and cardiac catheter measurements.MethodsThis study included 25 patients (17 males, and 8 females; a median age of 2 years, range: 4 months–4 years) with CHD. All patients underwent both transthoracic echocardiography (TTE) and MDCTA within 2 weeks prior to cardiac catheterization. CFD models were created from MDCTA raw data. Boundary conditions were confirmed by lumped parameter model and transthoracic echocardiography (TTE). Peak systolic velocity derived from CFD models (PSVCFD) was compared to TTE measurements (PSVTTE), while the peak systolic pressure derived from CFD (PSPCFD) was compared to catheterization (PSPCC). Regions with low and high peak systolic wall shear stress (PSWSS) were also evaluated.ResultsPSVCFD and PSPCFD showed good agreements between PSVTTE (r = 0.968, p < 0.001; mean bias = − 7.68 cm/s) and PSPCC (r = 0.918, p < 0.001; mean bias = 1.405 mmHg). Regions with low and high PSWSS) can also be visualized. Skewing of velocity or helical blood flow was also observed at aortic arch in patients.ConclusionsOur result demonstrated that CFD scheme based on MDCTA raw data is an accurate and convenient method in obtaining the velocity and pressure from aorta and displaying the distribution of PSWSS and flow pattern of aorta. The preliminary results from our study demonstrate the capability in combining clinical imaging data and novel CFD tools in infants with CHD and provide a noninvasive approach for diagnose of CHD such as coarctation of aorta in future.

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Genomic imbalances in syndromic congenital heart disease

Abstract: These data showed that patients presenting CHD with extra cardiac anomalies and exclusion of 22q11.2 DS should be investigated by CMA. The present study emphasizes the possible role of CNVs in CHD.

Cited by 30 publications

References 28 publications

Genetic Imbalances in Argentinean Patients with Congenital Conotruncal Heart Defects

Genetic Imbalances in Argentinean Patients with Congenital Conotruncal Heart Defects

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

Clinical validation and assessment of aortic hemodynamics using computational fluid dynamics simulations from computed tomography angiography

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