ArticleG3 (Bethesda, Md.)2016
A HAND2 Loss-of-Function Mutation Causes Familial Ventricular Septal Defect and Pulmonary Stenosis.
Article in G3 (Bethesda, Md.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- Twenty-Five Novel Loci for Carotid Intima-Media Thickness: A Genome-Wide Association Study in >45 000 Individuals and Meta-Analysis of >100 000 Individuals.Arteriosclerosis, thrombosis, and vascular biology · 2022Pooled it
- Endocardial transcription factor HAND2 orchestrates hypoxic and TGF-β signaling to modulate coronary artery formation.The Journal of clinical investigation · 2026Article
- Rare TruncatingGenes · 2026Article
- Exploration of candidate genes associated with rare SNVs in pulmonary stenosis using whole-exome sequencing and machine learning.Frontiers in genetics · 2026Article
- In Vivo Models of Cardiovascular Disease:Biomedicines · 2025Review
- Characterization of an induced pluripotent stem cell line NCHi025-A from a 1-year-old female with pulmonary stenosis harboring a heterozygous HAND2 variant.Stem cell research · 2025Article
- PDGFRA is a conserved HAND2 effector during early cardiac development.Nature cardiovascular research · 2024Article
- HAND factors regulate cardiac lineage commitment and differentiation from human pluripotent stem cells.Stem cell research & therapy · 2024Article
- [Association of ventricular septal defect with rare variations of theZhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2023Article
- The adult heart requires baseline expression of the transcription factor Hand2 to withstand right ventricular pressure overload.Cardiovascular research · 2022Article
- Delving into the Molecular World of Single Ventricle Congenital Heart Disease.Current cardiology reports · 2022Review
- Bmp Signaling Regulates Hand1 in a Dose-Dependent Manner during Heart Development.International journal of molecular sciences · 2021Article
- Genetics of congenital heart disease: a narrative review of recent advances and clinical implications.Translational pediatrics · 2021Review
- Deletion ofCold Spring Harbor molecular case studies · 2021Article
- Transcriptional Regulation of Postnatal Cardiomyocyte Maturation and Regeneration.International journal of molecular sciences · 2021Review
- Understanding Heart Field Progenitor Cells for Modeling Congenital Heart Diseases.Current cardiology reports · 2021Review
- Evolutionary transcriptomics implicateseLife · 2021Article
- Cardiac NaScience China. Life sciences · 2021Article
- Genetic Basis of Human Congenital Heart Disease.Cold Spring Harbor perspectives in biology · 2020Article
- The genetics of isolated congenital heart disease.American journal of medical genetics. Part C, Seminars in medical genetics · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Congenital heart disease (CHD) is the most common developmental abnormality, and is the leading noninfectious cause of mortality in neonates. Increasing evidence demonstrates that genetic defects play an important role in the pathogenesis of CHD. However, CHD exhibits substantial heterogeneity, and the genetic determinants for CHD remain unknown in the overwhelming majority of cases. In the current study, the coding exons and flanking introns of the HAND2 gene, which encodes a basic helix-loop-helix transcription factor essential for normal cardiovascular development, were sequenced in 192 unrelated patients with CHD, and a novel heterozygous mutation, p.S65I, was identified in a patient with congenital ventricular septal defect (VSD). Genetic analysis of the index patient's pedigree revealed that the mutation was present in all seven affected family members available, but absent in the 13 unaffected family members examined. Besides, in addition to VSD, five of the proband's close relatives also had pulmonary stenosis (PS), and the proband's son also had double outlet right ventricle (DORV). The missense mutation, which altered an evolutionarily conserved amino acid, was absent in 300 unrelated, ethnically matched healthy individuals. Biological analyses using a dual-luciferase reporter assay system showed that the mutant HAND2 was associated with significantly diminished transcriptional activity. Furthermore, the mutation abolished the synergistic activation between HAND2 and GATA4, as well as NKX2.5-two other cardiac core transcriptional factors that have been causally linked to CHD. These findings indicate that HAND2 loss-of-function mutation contributes to human CHD, perhaps via its interaction with GATA4 and NKX2.5.
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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.