Browse
Submit Data
Databases
API
Help

Dataset Information

16 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Deep Phenotypic Analysis for Transposition of the Great Arteries and Prognosis Implication.

ABSTRACT: 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.

SUBMITTER: Shen H

PROVIDER: S-EPMC9238490 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Anatomically corrected malposed great arteries misdiagnosed as transposition of great arteries: Diagnosis on fetal echocardiography.

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

Transplantation after Mustard operation for transposition of the great arteries.

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

The phenotypic spectrum of ZIC3 mutations includes isolated d-transposition of the great arteries and double outlet right ventricle.

Project description:Disease causing mutations for heterotaxy syndrome were first identified in the X-linked laterality gene, ZIC3. Mutations typically result in males with situs ambiguus and complex congenital heart disease; however affected females and one male with isolated d-transposition of the great arteries (d-TGA) have been reported. We hypothesized that a subset of patients with heart defects common to heterotaxy but without laterality defects would have ZIC3 mutations. We also sought to estimate the prevalence of ZIC3 mutations in sporadic heterotaxy. Patients with TGA (n = 169), double outlet right ventricle (DORV; n = 89), common atrioventricular canal (CAVC; n = 41), and heterotaxy (n = 54) underwent sequencing of ZIC3 exons. We tested 90 patients with tetralogy of Fallot (TOF) to correlate genotype with phenotype. Three potentially disease-related missense mutations were detected: c.49G > T (Gly17Cys) in a female with isolated DORV, c.98C > T (Ala33Val) in a male with isolated d-TGA, and c.841C > T (His281Tyr) in a female with sporadic heterotaxy. We also identified a novel insertion (CPFP333ins) in a family with heterotaxy. All were absent in 200 control patients and the 1000 Genomes Project (n = 629). No significant mutations were found in patients with TOF. Functional studies demonstrated reduced transcriptional activity of the ZIC3 His281Tyr mutant protein. ZIC3 mutations were rarely identified in isolated DORV and d-TGA suggesting that a subset of DORV and d-TGA may fall within the spectrum of laterality defects. ZIC3 mutations were found in 3.7% of patients with sporadic heterotaxy; therefore testing should be considered in patients with heterotaxy.

| S-EPMC3707401 | biostudies-literature

Transposition of the great arteries - a phenotype associated with 16p11.2 duplications?

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

Coronary Artery Aneurysms Following Repair of Transposition of the Great Arteries.

Project description: Not available

| S-EPMC10954681 | biostudies-literature

Human 3p14.3: A Regulatory Region in Transposition of the Great Arteries.

Project description: Not available

| S-EPMC8852236 | biostudies-literature

Common Genetic Variants Contribute to Risk of Transposition of the Great Arteries.

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

Prenatal diagnosis of transposition of great arteries with left anterior aorta (SDL-TGA).

Project description:We report a case with prenatal diagnosis of transposition of great arteries (TGA) with L-posed aorta (SDL-TGA) which was confirmed by postnatal echocardiography. The anatomic findings were confirmed during the successful arterial switch operation (ASO). The technical challenges of ASO in the L-posed aorta are also described.

| S-EPMC10015403 | biostudies-literature

Modeling Transposition of the Great Arteries with Patient-Specific Induced Pluripotent Stem Cells.

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

Streaming in transposition of the great arteries by using cardiac magnetic resonance imaging.

Project description: Not available

| S-EPMC4050289 | biostudies-literature