Identification of Copy Number Variations in Isolated Tetralogy of Fallot

Aguayo-Gómez, Adolfo; Arteaga‐Vázquez, Jazmín; Svyryd, Yevgeniya; Calderón‐Colmenero, Juan; Zamora-González, Carlos; Vargas‐Alarcón, Gilberto; Mutchinick, Osvaldo M.

doi:10.1007/s00246-015-1210-9

Cited by 13 publications

(13 citation statements)

References 26 publications

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“…This finding agrees with the previous reports, where detection rate range from 0.4 to 8.5%. 11,[13][14][15]18 22q11DupS identification is reported less commonly, ranging from 0.7 to 2.5%, 13,14,16 very similar to our own (0.5%). Identification of 22q11DupS has been increased due to screening techniques currently used.…”

Section: Discussionsupporting

confidence: 86%

GATA4 Deletions Associated with Congenital Heart Diseases in South Brazil

et al. 2020

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The normal development of the heart comprises a highly regulated machinery of genetic events, involving transcriptional factors. Congenital heart disease (CHD), have been associated with chromosomal abnormalities and copy number variants (CNVs). Our goal was to investigate through the multiplex ligation-dependent probe amplification (MLPA) technique, the presence of CNVs in reference genes for normal cardiac development in patients with CHD. GATA4, NKX2–5, TBX5, BMP4, and CRELD1 genes and 22q11.2 chromosome region were analyzed in 207 children with CHD admitted for the first time in a cardiac intensive care unit from a pediatric hospital. CNVs were detected in seven patients (3.4%): four had a 22q11.2 deletion (22q11DS) (1.9%), two had a GATA4 deletion (1%) and one had a 22q11.2 duplication (0.5%). No patients with CNVs in the NKX2–5, TBX5, BMP4, and CRELD1 genes were identified. GATA4 deletions appear to be present in a significant number of CHD patients, especially those with septal defects, persistent left superior vena cava, pulmonary artery abnormalities, and extracardiac findings. GATA4 screening seems to be more effective when directed to these CHDs. The investigation of CNVs in GATA4 and 22q11 chromosome region in patients with CHD is important to anticipating the diagnosis, and to contributing to family planning.

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Section: Discussionsupporting

confidence: 86%

GATA4 Deletions Associated with Congenital Heart Diseases in South Brazil

et al. 2020

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“…The results showed that the expression of human GATA4, NKX2.5, TBX1, HAND2, SMYD1 and MEF2C was significantly downregulated compared with that in the control ( Fig. 2A-F), which is similar to the cases for GATA4, NKX2.5 and TBX1 observed in other studies 28,29 . Compared with the control samples, the mean expression of ISL1 was higher than that of the control group, which was significant ( Fig.…”

Section: Resultssupporting

confidence: 85%

BVES downregulation in non-syndromic tetralogy of fallot is associated with ventricular outflow tract stenosis

Shi

Wang

et al. 2020

Sci Rep

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BVES is a transmembrane protein, our previous work demonstrated that single nucleotide mutations of BVES in tetralogy of fallot (TOF) patients cause a downregulation of BVES transcription. However, the relationship between BVES and the pathogenesis of TOF has not been determined. Here we reported our research results about the relationship between BVES and the right ventricular outflow tract (RVOT) stenosis. BVES expression was significantly downregulated in most TOF samples compared with controls. The expression of the second heart field (SHF) regulatory network genes, including NKX2.5, GATA4 and HAND2, was also decreased in the TOF samples. In zebrafish, bves knockdown resulted in looping defects and ventricular outflow tract (VOT) stenosis, which was mostly rescued by injecting bves mRNA. bves knockdown in zebrafish also decreased the expression of SHF genes, such as nkx2.5, gata4 and hand2, consistent with the TOF samples` results. The dualfluorescence reporter system analysis showed that BVES positively regulated the transcriptional activity of GATA4, NKX2.5 and HAND2 promoters. In zebrafish, nkx2.5 mRNA partially rescued VOT stenosis caused by bves knockdown. These results indicate that BVES downregulation may be associated with RVOT stenosis of non-syndromic TOF, and bves is probably involved in the development of VOT in zebrafish. Congenital heart disease (CHD) is the most common birth defect, exhibiting a mortality rate of more than 29% 1. Within this group of conditions, the incidence of TOF is 7-10% in the USA 2 , 13.4% in Nigeria 3 , and 16% in India 4. However, the aetiology of TOF has not been fully elucidated. Anatomically, TOF has four distinct structural defects, namely, ventricular septal defect, overriding of the aorta, RVOT/pulmonary artery (PA) stenosis and right ventricular hypertrophy 5. However, embryologically, the defects are thought to be caused by a single developmental error, involving the outflow tract funnel septum shifting left to right or forward, leading to a poor contraposition ventricular septal defect, overriding of the aorta and RVOT funnel stenosis 5-11. RVOT stenosis eventually leads to right ventricular hypertrophy 10. The degree of RVOT stenosis is a key clinical factor for the diagnosis of TOF 10. However, the molecular mechanism behind RVOT/PA stenosis remains under investigation. The development of the cardiac outflow tract has two major cell sources: one is neural crest cells, which provide cells for the distal development of the great artery by migration, while releasing signals to the SHF 7 ; the other

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“…NuRD complex target specificity can be conferred by the association of components of the NuRD complex with tissue-specific cofactors that target the complex to a defined set of loci. Factors include three proteins associated with congenital heart disease: FOG-2, TBX5, and TBX20 ( 3 , 19 – 32 ). Consistently, mutations in CHD4 have been found to be causative to congenital heart disease, including atrial and ventricular septal defects ( 4 ).…”

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confidence: 99%

CHD4 and the NuRD complex directly control cardiac sarcomere formation

Wilczewski

Hepperla

Shimbo

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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SignificanceBirth defects are the leading cause of infant mortality in the United States and Europe, with cardiac defects being the most prevalent. Here we define the requirement and mechanism of action of CHD4, the catalytic core component of the nucleosome remodeling and deacetylase (NuRD) complex, in embryonic heart development. CHD4 is essential from fly to human and mutations in CHD4 are causative to congenital heart disease, including atrial and ventricular septal defects. By generating a cardiac conditional null allele of CHD4, temporal transcriptional profiling, and systems-level analysis of CHD4 target genes and in utero echocardiography, we define molecular, biochemical, anatomical, and physiological mechanisms for CHD4 and the NuRD complex in repressing inappropriate expression of the skeletal and smooth muscle programs in the developing heart.

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Identification of Copy Number Variations in Isolated Tetralogy of Fallot

Cited by 13 publications

References 26 publications

GATA4 Deletions Associated with Congenital Heart Diseases in South Brazil

GATA4 Deletions Associated with Congenital Heart Diseases in South Brazil

BVES downregulation in non-syndromic tetralogy of fallot is associated with ventricular outflow tract stenosis

CHD4 and the NuRD complex directly control cardiac sarcomere formation

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