ArticleEuropean journal of human genetics : EJHG2013
A variant in the carboxyl-terminus of connexin 40 alters GAP junctions and increases risk for tetralogy of Fallot.
Article in European journal of human genetics : EJHG, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 44 citations in OpenAlex.
- Disrupted transcriptional networks regulated by CHD1L during neurodevelopment underlie the mirrored neuroanatomical and growth phenotypes of the 1q21.1 copy number variant.Nucleic acids research · 2025Article
- Prenatal diagnosis of the recurrent 1q21.1 microdeletions in fetuses with ultrasound anomalies and review of the literature.Frontiers in genetics · 2024Article
- Genetic and ultrasonographic analyses of fetuses with 1q21.1q21.2 microdeletion/microduplication: a retrospective study.BMC medical genomics · 2023Article
- Prenatal phenotypes and pregnancy outcomes of fetuses with recurrent 1q21.1 microdeletions and microduplications.Frontiers in medicine · 2023Article
- Genetics of congenital heart disease: a narrative review of recent advances and clinical implications.Translational pediatrics · 2021Review
- Detection of copy number variation associated with ventriculomegaly in fetuses using single nucleotide polymorphism arrays.Scientific reports · 2021Article
- Importance of Cx43 for Right Ventricular Function.International journal of molecular sciences · 2021Review
- Case Report: Neuroblastoma Breakpoint Family Genes Associate With 1q21 Copy Number Variation Disorders.Frontiers in genetics · 2021Article
- Brain Disorders and Chemical Pollutants: A Gap Junction Link?Biomolecules · 2020Review
- Conjugated activation of myocardial-specific transcription of Gja5 by a pair of Nkx2-5-Shox2 co-responsive elements.Developmental biology · 2020Article
- Genetic Basis for Congenital Heart Disease: Revisited: A Scientific Statement From the American Heart Association.Circulation · 2018Review
- Clinical and molecular cytogenetic analyses of four families with 1q21.1 microdeletion or microduplication.The journal of gene medicine · 2017Article
- Rare copy number variants in patients with congenital conotruncal heart defects.Birth defects research · 2017Article
- Article
- Existence of mutations in the homeodomain-encoding region of NKX2.5 gene in Iranian patients with tetralogy of Fallot.Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences · 2016Article
- What Is New in Genetics of Congenital Heart Defects?Frontiers in pediatrics · 2016Review
- 1q21.1 microduplication in a patient with mental impairment and congenital heart defect.Molecular medicine reports · 2015Article
- Phenotypic Variability Associated with a Large Recurrent 1q21.1 Microduplication in a Three-Generation Family.Molecular syndromology · 2015Article
- Parental occupational exposures to endocrine disruptors and the risk of simple isolated congenital heart defects.Pediatric cardiology · 2015Article
- Tetralogy of Fallot and Hypoplastic Left Heart Syndrome - Complex Clinical Phenotypes Meet Complex Genetic Networks.Current genomics · 2015Article
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Authors and funding
16 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
GJA5 gene (MIM no. 121013), localized at 1q21.1, encodes for the cardiac gap junction protein connexin 40. In humans, copy number variants of chromosome 1q21.1 have been associated with variable phenotypes comprising congenital heart disease (CHD), including isolated TOF. In mice, the deletion of Gja5 can cause a variety of complex CHDs, in particular of the cardiac outflow tract, corresponding to TOF in many cases. In the present study, we screened for mutations in the GJA5 gene 178 unrelated probands with isolated TOF. A heterozygous nucleotide change (c.793C>T) in exon 2 of the gene leading to the p.Pro265Ser variant at the carboxyl-terminus of the protein was found in two unrelated sporadic patients, one with classic anatomy and one with pulmonary atresia. This GJA5 missense substitution was not observed in 1568 ethnically-matched control chromosomes. Immunofluorescent staining and confocal microscopy revealed that cells expressing the mutant protein form sparse or no visible gap-junction plaques in the region of cell-cell contact. Moreover, analysis of the transfer of the gap junction permanent tracer lucifer yellow showed that cells expressing the mutant protein have a reduced rate of dye transfer compared with wild-type cells. Finally, use of a zebrafish model revealed that microinjection of the GJA5-p.Pro265Ser mutant disrupts overall morphology of the heart tube in the 37% (22/60) of embryos, compared with the 6% (4/66) of the GJA5 wild-type-injected embryos. These findings implicate GJA5 gene as a novel susceptibility gene for TOF.
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