ArticlePloS one2015
PITX2 Loss-of-Function Mutation Contributes to Congenital Endocardial Cushion Defect and Axenfeld-Rieger Syndrome.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 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
21 citing papers in PubMed, 40 citations in OpenAlex.
- Application of Prenatal Whole Exome Sequencing for Congenital Heart Anomalies.International journal of molecular sciences · 2026Review
- Single-Nucleotide Polymorphisms,International journal of molecular sciences · 2025Review
- Single-nuclei multiomics analysis identifies abnormal cardiomyocytes in a murine model of cardiac development.Nature communications · 2025Article
- In Silico Characterization of Pathogenic Homeodomain Missense Mutations in the PITX2 Gene.Biochemical genetics · 2025Article
- Review
- UNC-30/PITX coordinates neurotransmitter identity with postsynaptic GABA receptor clustering.Development (Cambridge, England) · 2024Article
- Zebrafish Congenital Heart Disease Models: Opportunities and Challenges.International journal of molecular sciences · 2024Review
- Human Genetics of d-Transposition of Great Arteries.Advances in experimental medicine and biology · 2024Review
- Case report: Congenital mitral and tricuspid valve insufficiency in a patient with Axenfeld-Rieger syndrome.Frontiers in cardiovascular medicine · 2022Article
- Mechanistic Insights into Axenfeld-Rieger Syndrome from ZebrafishInternational journal of molecular sciences · 2021Review
- Genetics of Transposition of Great Arteries: Between Laterality Abnormality and Outflow Tract Defect.Journal of cardiovascular translational research · 2021Review
- Pitx genes in development and disease.Cellular and molecular life sciences : CMLS · 2021Review
- Unusual association of Axenfeld-Rieger syndrome and wandering spleen: A case report.World journal of clinical cases · 2020Article
- Genetics of Congenital Heart Disease.Biomolecules · 2019Review
- Novel PITX2 Mutations including a Mutation Causing an Unusual Ophthalmic Phenotype of Axenfeld-Rieger Syndrome.Journal of ophthalmology · 2019Article
- Multiple Roles of Pitx2 in Cardiac Development and Disease.Journal of cardiovascular development and disease · 2017Review
- HAND1 Loss-of-Function Mutation Causes Tetralogy of Fallot.Pediatric cardiology · 2017Article
- A Novel Mutation inMolecular syndromology · 2017Article
- Current Perspectives in Cardiac Laterality.Journal of cardiovascular development and disease · 2016Review
- The Dorsal Mesenchymal Protrusion and the Pathogenesis of Atrioventricular Septal Defects.Journal of cardiovascular development and disease · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Congenital heart disease (CHD), the most common type of birth defect, is still the leading non-infectious cause of infant morbidity and mortality in humans. Aggregating evidence demonstrates that genetic defects are involved in the pathogenesis of CHD. However, CHD is genetically heterogeneous and the genetic components underpinning CHD in an overwhelming majority of patients remain unclear. In the present study, the coding exons and flanking introns of the PITX2 gene, which encodes a paired-like homeodomain transcription factor 2essential for cardiovascular morphogenesis as well as maxillary facial development, was sequenced in 196 unrelated patients with CHD and subsequently in the mutation carrier's family members available. As a result, a novel heterozygous PITX2 mutation, p.Q102X for PITX2a, or p.Q148X for PITX2b, or p.Q155X for PITX2c, was identified in a family with endocardial cushion defect (ECD) and Axenfeld-Rieger syndrome (ARS). Genetic analysis of the pedigree showed that the nonsense mutation co-segregated with ECD and ARS transmitted in an autosomal dominant pattern with complete penetrance. The mutation was absent in 800 control chromosomes from an ethnically matched population. Functional analysis by using a dual-luciferase reporter assay system revealed that the mutant PITX2 had no transcriptional activity and that the mutation eliminated synergistic transcriptional activation between PITX2 and NKX2.5, another transcription factor pivotal for cardiogenesis. To our knowledge, this is the first report on the association of PITX2 loss-of-function mutation with increased susceptibility to ECD and ARS. The findings provide novel insight into the molecular mechanisms underpinning ECD and ARS, suggesting the potential implications for the antenatal prophylaxis and personalized treatment of CHD and ARS.
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.