ArticlePLoS genetics2016
Family Based Whole Exome Sequencing Reveals the Multifaceted Role of Notch Signaling in Congenital Heart Disease.
Article in PLoS genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
What it found
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Who cites it
45 citing papers in PubMed, 68 citations in OpenAlex.
- Aberrant Phase Separation of Endothelial MAML1 Causes Congenital Heart Disease by Suppressing Notch Activity.Circulation · 2026Article
- Placental vascular abnormality is associated with worse neurodevelopmental outcomes for infants with congenital heart disease and genetic abnormality.Early human development · 2026Article
- Decoding human cardiovascular development and disease through single-cell transcriptomic and epigenomic profiling.Trends in cell biology · 2025Review
- Bicuspid Aortic Valve and Sudden Cardiac Death.Life (Basel, Switzerland) · 2025Review
- 2025 Heart Disease and Stroke Statistics: A Report of US and Global Data From the American Heart Association.Circulation · 2025Review
- Hereditary Aortopathies as Cause of Sudden Cardiac Death in the Young: State-of-the-Art Review in Molecular Medicine.Diseases (Basel, Switzerland) · 2024Review
- 2024 Heart Disease and Stroke Statistics: A Report of US and Global Data From the American Heart Association.Circulation · 2024Review
- In-Depth Genomic Analysis: The New Challenge in Congenital Heart Disease.International journal of molecular sciences · 2024Review
- Human Genetics of Ventricular Septal Defect.Advances in experimental medicine and biology · 2024Article
- Clinically Relevant Genetic Considerations for Patients With Tetralogy of Fallot.CJC pediatric and congenital heart disease · 2023Review
- Evaluating High-Confidence Genes in Conotruncal Cardiac Defects by Gene Burden Analyses.Journal of the American Heart Association · 2023Article
- Heart Disease and Stroke Statistics-2023 Update: A Report From the American Heart Association.Circulation · 2023Review
- Congenital aortic valve stenosis: from pathophysiology to molecular genetics and the need for novel therapeutics.Frontiers in cardiovascular medicine · 2023Review
- Disruption of the HIF-1 pathway in individuals with Ollier disease and Maffucci syndrome.PLoS genetics · 2022Article
- Investigation of Copy Number Variation in South African Patients With Congenital Heart Defects.Circulation. Genomic and precision medicine · 2022Article
- Considering the Genetic Architecture of Hypoplastic Left Heart Syndrome.Journal of cardiovascular development and disease · 2022Article
- Multifocal organoids reveal clonal associations between synchronous intestinal tumors with pervasive heterogeneous drug responses.NPJ genomic medicine · 2022Article
- Analysis of commonly expressed genes between first trimester fetal heart and placenta cell types in the context of congenital heart disease.Scientific reports · 2022Article
- Endocardial Regulation of Cardiac Development.Journal of cardiovascular development and disease · 2022Review
- Genomic frontiers in congenital heart disease.Nature reviews. Cardiology · 2022Review
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 3 countries.
Funding
Abstract
Left-ventricular outflow tract obstructions (LVOTO) encompass a wide spectrum of phenotypically heterogeneous heart malformations which frequently cluster in families. We performed family based whole-exome and targeted re-sequencing on 182 individuals from 51 families with multiple affected members. Central to our approach is the family unit which serves as a reference to identify causal genotype-phenotype correlations. Screening a multitude of 10 overlapping phenotypes revealed disease associated and co-segregating variants in 12 families. These rare or novel protein altering mutations cluster predominantly in genes (NOTCH1, ARHGAP31, MAML1, SMARCA4, JARID2, JAG1) along the Notch signaling cascade. This is in line with a significant enrichment (Wilcoxon, p< 0.05) of variants with a higher pathogenicity in the Notch signaling pathway in patients compared to controls. The significant enrichment of novel protein truncating and missense mutations in NOTCH1 highlights the allelic and phenotypic heterogeneity in our pediatric cohort. We identified novel co-segregating pathogenic mutations in NOTCH1 associated with left and right-sided cardiac malformations in three independent families with a total of 15 affected individuals. In summary, our results suggest that a small but highly pathogenic fraction of family specific mutations along the Notch cascade are a common cause of LVOTO.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.