SynthesisGenetics in medicine : official journal of the American College of Medical Genetics2021
Germline variants in HEY2 functional domains lead to congenital heart defects and thoracic aortic aneurysms.
Synthesis in Genetics in medicine : official journal of the American College of Medical Genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 13 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
13 citing papers in PubMed, 16 citations in OpenAlex.
- Defects inFrontiers in genetics · 2026Article
- The Expanding Genetic Architecture of Arteriopathies: From Canonical TAAD Genes to Emerging Connective Tissue and Signaling Pathways.Medical sciences (Basel, Switzerland) · 2025Review
- A novel heterozygous pathogenic variant in HEY2 led to a familial form of non-syndromic Tetralogy of Fallot.European journal of human genetics : EJHG · 2025Article
- The transcriptional repressor HEY2 regulates mitochondrial oxidative respiration to maintain cardiac homeostasis.Nature communications · 2025Article
- Article
- SomaticExperimental and therapeutic medicine · 2024Article
- Human Genetics of Ventricular Septal Defect.Advances in experimental medicine and biology · 2024Article
- Discovery ofAmerican journal of translational research · 2024Article
- The Roles of Histone Lysine Methyltransferases in Heart Development and Disease.Journal of cardiovascular development and disease · 2023Review
- Discovery ofBiology · 2023Article
- Study of variants associated with ventricular septal defects (VSDs) highlights the unique genetic structure of the Pakistani population.Italian journal of pediatrics · 2022Article
- Integrative analysis of genomic variants reveals new associations of candidate haploinsufficient genes with congenital heart disease.PLoS genetics · 2021Article
- Pathways Regulating Establishment and Maintenance of Cardiac Chamber Identity in Zebrafish.Journal of cardiovascular development and disease · 2021Review
Corrections and comments
- Erratum issued
Authors and funding
26 authors at 11 institutions in 4 countries.
Funding
Abstract
purposeIn this study we aimed to establish the genetic cause of a myriad of cardiovascular defects prevalent in individuals from a genetically isolated population, who were found to share a common ancestor in 1728.
methodsTrio genome sequencing was carried out in an index patient with critical congenital heart disease (CHD); family members had either exome or Sanger sequencing. To confirm enrichment, we performed a gene-based association test and meta-analysis in two independent validation cohorts: one with 2685 CHD cases versus 4370 . These controls were also ancestry-matched (same as FTAA controls), and the other with 326 cases with familial thoracic aortic aneurysms (FTAA) and dissections versus 570 ancestry-matched controls. Functional consequences of identified variants were evaluated using expression studies.
resultsWe identified a loss-of-function variant in the Notch target transcription factor-encoding gene HEY2. The homozygous state (n = 3) causes life-threatening congenital heart defects, while 80% of heterozygous carriers (n = 20) had cardiovascular defects, mainly CHD and FTAA of the ascending aorta. We confirm enrichment of rare risk variants in HEY2 functional domains after meta-analysis (MetaSKAT p = 0.018). Furthermore, we show that several identified variants lead to dysregulation of repression by HEY2.
conclusionA homozygous germline loss-of-function variant in HEY2 leads to critical CHD. The majority of heterozygotes show a myriad of cardiovascular defects.
Indexed as
Identifiers
What OpenQuestion holds
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.