ArticleHuman molecular genetics2020
Functional characterization of a novel PBX1 de novo missense variant identified in a patient with syndromic congenital heart disease.
Article in Human molecular genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 32 citations in OpenAlex.
- Assessing the contribution of rare variants to congenital heart disease through a large-scale case-control exome study.NPJ genomic medicine · 2026Article
- Analyzing the genetic profile of autistic children and adolescents with minimal verbal abilities.Frontiers in genetics · 2026Article
- Unveiling complex patterns: An information-theoretic approach to high-order behaviors in microarray data.PloS one · 2025Article
- Review
- Understanding the Genetic and Non-Genetic Interconnections in the Aetiology of Syndromic Congenital Heart Disease: An Updated Review: Part 2.Current cardiology reports · 2024Review
- Prdm16 mutation determines sex-specific cardiac metabolism and identifies two novel cardiac metabolic regulators.Cardiovascular research · 2024Article
- Application and perspective of CRISPR/Cas9 genome editing technology in human diseases modeling and gene therapy.Frontiers in genetics · 2024Review
- Comprehensive summary: the role of PBX1 in development and cancers.Frontiers in cell and developmental biology · 2024Review
- Comprehensive overview of the role of PBX1 in mammalian kidneys.Frontiers in molecular biosciences · 2023Review
- Genome Editing and Myocardial Development.Advances in experimental medicine and biology · 2023Review
- Identification ofDiagnostics (Basel, Switzerland) · 2022Article
- The regulation of PBXs and their emerging role in cancer.Journal of cellular and molecular medicine · 2022Review
- SOX7 loss-of-function variation as a cause of familial congenital heart disease.American journal of translational research · 2022Article
- PBX1: a key character of the hallmarks of cancer.Journal of molecular medicine (Berlin, Germany) · 2021Review
- Genetic and Metabolic Determinants of Atrial Fibrillation in a General Population Sample: The CHRIS Study.Biomolecules · 2021Article
- Application of CRISPR-Cas9 gene editing for congenital heart disease.Clinical and experimental pediatrics · 2021Article
- Case Report: Candidate Genes Associated With Prenatal Ultrasound Anomalies in a Fetus With Prenatally Detected 1q23.3q31.2 Deletion.Frontiers in genetics · 2021Article
- Review
- Paternal mosaicism for a novel PBX1 mutation associated with recurrent perinatal death: Phenotypic expansion of the PBX1-related syndrome.American journal of medical genetics. Part A · 2020Article
- Myhre syndrome is caused by dominant-negative dysregulation of SMAD4 and other co-factors.Differentiation; research in biological diversityArticle
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
Pre-B cell leukemia factor 1 (PBX1) is an essential developmental transcription factor, mutations in which have recently been associated with CAKUTHED syndrome, characterized by multiple congenital defects including congenital heart disease (CHD). During analysis of a whole-exome-sequenced cohort of heterogeneous CHD patients, we identified a de novo missense variant, PBX1:c.551G>C p.R184P, in a patient with tetralogy of Fallot with absent pulmonary valve and extra-cardiac phenotypes. Functional analysis of this variant by creating a CRISPR-Cas9 gene-edited mouse model revealed multiple congenital anomalies. Congenital heart defects (persistent truncus arteriosus and ventricular septal defect), hypoplastic lungs, hypoplastic/ectopic kidneys, aplastic adrenal glands and spleen, as well as atretic trachea and palate defects were observed in the homozygous mutant embryos at multiple stages of development. We also observed developmental anomalies in a proportion of heterozygous embryos, suggestive of a dominant mode of inheritance. Analysis of gene expression and protein levels revealed that although Pbx1 transcripts are higher in homozygotes, amounts of PBX1 protein are significantly decreased. Here, we have presented the first functional model of a missense PBX1 variant and provided strong evidence that p.R184P is disease-causal. Our findings also expand the phenotypic spectrum associated with pathogenic PBX1 variants in both humans and mice.
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