Human 3p14.3: A Regulatory Region in Transposition of the Great Arteries.
Ontology highlight
ABSTRACT:
SUBMITTER: Cashman TJ
PROVIDER: S-EPMC8852236 | biostudies-literature | 2022 Jan
REPOSITORIES: biostudies-literature
Publications
Human 3p14.3: A Regulatory Region in Transposition of the Great Arteries.
Cashman Timothy J TJ Trivedi Chinmay M CM
Circulation research 20220120 2
Similar Datasets
Project description:We present a diagnosis of isolated anatomically corrected malposed great arteries on fetal echocardiography at 31 weeks of gestation period. The patient was referred to our institute with a diagnosis of suspected transposition of great arteries.
| S-EPMC5007939 | biostudies-literature
Project description: Not available
| S-EPMC4900386 | biostudies-literature
Project description:As long-term outcomes of congenital heart diseases improve, the probability of adult patients presenting for heart transplantation for late failure of congenitally corrected heart disease also increases. In patients with dextro-transposition of the great arteries (d-TGA) who were initially treated in the era of Mustard or Senning procedures and before Jatene procedure was introduced, progressive systemic right ventricular failure represents a problem in the very long-term follow-up. We report a rare case of heart transplantation as a third operation 36 years after Mustard procedure in a patient with d-TGA experiencing late failure of the systemic right ventricle.
| S-EPMC8502455 | biostudies-literature
Project description:BackgroundPITX2 is a bicoid-related homeodomain transcription factor that plays an important role in asymmetric cardiogenesis. Loss of function experiments in mice cause severe heart malformations, including transposition of the great arteries (TGA). TGA accounts for 5-7% of all congenital heart diseases affecting 0.2 per 1000 live births, thereby representing the most frequent cyanotic heart defect diagnosed in the neonatal period.MethodsTo address whether altered PITX2 function could also contribute to the formation of dTGA in humans, we screened 96 patients with dTGA by means of dHPLC and direct sequencing for mutations within the PITX2 gene.ResultsSeveral SNPs could be detected, but no stop or frame shift mutation. In particular, we found seven intronic and UTR variants, two silent mutations and two polymorphisms within the coding region.ConclusionAs most sequence variants were also found in controls we conclude that mutations in PITX2 are not a common cause of dTGA.
| S-EPMC1142516 | biostudies-literature
Project description:Genetic analyses of patients with transposition of the great arteries have identified rare copy number variations, suggesting that they may be significant to the aetiology of the disease. This paper reports the identification of a 16p11.2 microduplication, a variation that has yet to be reported in association with transposition of the great arteries. The 16p11.2 microduplication is associated with autism spectrum disorder and developmental delay, but with highly variable phenotypic effects. Autism and attention deficit disorders are observed more frequently in children with congenital heart disease than in the general population. Neonatal surgery is proposed as a risk factor, but as yet unidentified genetic abnormalities should also be taken into account. Thus, congenital heart abnormalities may constitute a part of the phenotypic spectrum associated with duplications at 16p11.2. We suggest chromosomal microarray be considered part of the diagnostic work-up in patients with transposition of the great arteries.
| S-EPMC5746628 | biostudies-literature
Project description: Not available
| S-EPMC10954681 | biostudies-literature
Project description: Not available
| S-EPMC5412735 | biostudies-literature
Project description:Background Transposition of the great arteries (TGA) consists of about 3% of all congenital heart diseases and 20% of cyanotic congenital heart diseases. It is always accompanied by a series of other cardiac malformations that affect the surgical intervention strategy as well as prognosis. In this study, we comprehensively analyzed the phenotypes of the patients who had TGA with concordant atrioventricular and discordant ventriculoarterial connections and explored their association with prognosis. Methods and Results We retrospectively reviewed 666 patients with a diagnosis of TGA with concordant atrioventricular and discordant ventriculoarterial connections in Fuwai Hospital from 1997 to 2019. Under the guidance of the Human Phenotype Ontology database, patients were classified into 3 clusters. The Kaplan-Meier method was used to analyze the prognosis, and the Cox proportional regression model was used to investigate the risk factors. In this 666-patient TGA cohort, the overall 5-year survival rate was 94.70% (92.95%-96.49%). Three clusters with distinct phenotypes were obtained by the Human Phenotype Ontology database. Kaplan-Meier analysis revealed a significant difference in freedom from reintervention among 3 clusters (P<0.001). To eliminate the effect of surgeries, we analyzed patients who only received an arterial switch operation and still found a significant difference in reintervention (P=0.019). Conclusions We delineated a big cardiovascular phenotypic profile of an unprecedentedly large TGA cohort and successfully risk stratified them to reveal prognostic significance. Also, we reported the outcomes of a large TGA population in China.
| S-EPMC9238490 | biostudies-literature
Project description:RationaleDextro-transposition of the great arteries (D-TGA) is a severe congenital heart defect which affects approximately 1 in 4,000 live births. While there are several reports of D-TGA patients with rare variants in individual genes, the majority of D-TGA cases remain genetically elusive. Familial recurrence patterns and the observation that most cases with D-TGA are sporadic suggest a polygenic inheritance for the disorder, yet this remains unexplored.ObjectiveWe sought to study the role of common single nucleotide polymorphisms (SNPs) in risk for D-TGA.Methods and resultsWe conducted a genome-wide association study in an international set of 1,237 patients with D-TGA and identified a genome-wide significant susceptibility locus on chromosome 3p14.3, which was subsequently replicated in an independent case-control set (rs56219800, meta-analysis P=8.6x10-10, OR=0.69 per C allele). SNP-based heritability analysis showed that 25% of variance in susceptibility to D-TGA may be explained by common variants. A genome-wide polygenic risk score derived from the discovery set was significantly associated to D-TGA in the replication set (P=4x10-5). The genome-wide significant locus (3p14.3) co-localizes with a putative regulatory element that interacts with the promoter of WNT5A, which encodes the Wnt Family Member 5A protein known for its role in cardiac development in mice. We show that this element drives reporter gene activity in the developing heart of mice and zebrafish and is bound by the developmental transcription factor TBX20. We further demonstrate that TBX20 attenuates Wnt5a expression levels in the developing mouse heart.ConclusionsThis work provides support for a polygenic architecture in D-TGA and identifies a susceptibility locus on chromosome 3p14.3 near WNT5A. Genomic and functional data support a causal role of WNT5A at the locus.
| S-EPMC8768504 | biostudies-literature
Project description:The dextro-transposition of the great arteries (d-TGA) is one of the most common congenital heart diseases. To identify biological processes that could be related to the development of d-TGA, we established induced pluripotent stem cell (iPSC) lines from two patients with d-TGA and from two healthy subjects (as controls) and differentiated them into endothelial cells (iPSC-ECs). iPSC-EC transcriptome profiling and bioinformatics analysis revealed differences in the expression level of genes involved in circulatory system and animal organ development. iPSC-ECs from patients with d-TGA showed impaired ability to develop tubular structures in an in vitro capillary-like tube formation assay, and interactome studies revealed downregulation of biological processes related to Notch signaling, circulatory system development and angiogenesis, pointing to alterations in vascular structure development. Our study provides an iPSC-based cellular model to investigate the etiology of d-TGA.
| S-EPMC8705900 | biostudies-literature