Evidence map›Paper›PMID 41484984›Full record

ArticleHuman genomics2026

A precision medicine approach to interpret a GATA4 genetic variant in a paediatric patient with congenital heart disease.

Catherine A Forbes, Nicole C Shaw, Kevin G Chen, Mitchell Hedges, Teagan S Er, Livia Hool, Michelle Ward, Cathryn Poulton, Gareth Baynam, Timo Lassmann and 1 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in Human genomics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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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.

2 · The registry

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

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5 · Who and what money

Authors and funding

11 authors.

Catherine A Forbes *Translational Genetics, Precision Health, The Kids Research Institute Australia, Centre for Child Health Research, Perth Children's Hospital, The University of Western Australia, Nedlands, WA, 6009, Australia.
Nicole C Shaw *Translational Genetics, Precision Health, The Kids Research Institute Australia, Centre for Child Health Research, Perth Children's Hospital, The University of Western Australia, Nedlands, WA, 6009, Australia.
Kevin G ChenTranslational Genetics, Precision Health, The Kids Research Institute Australia, Centre for Child Health Research, Perth Children's Hospital, The University of Western Australia, Nedlands, WA, 6009, Australia.
Mitchell HedgesTranslational Genetics, Precision Health, The Kids Research Institute Australia, Centre for Child Health Research, Perth Children's Hospital, The University of Western Australia, Nedlands, WA, 6009, Australia.
Teagan S ErSchool of Human Sciences, The University of Western Australia, Crawley, WA, Australia.
Livia HoolSchool of Human Sciences, The University of Western Australia, Crawley, WA, Australia.
Michelle WardWestern Australian Register of Developmental Anomalies, King Edward Memorial Hospital, Subiaco, WA, Australia.
Cathryn PoultonUndiagnosed Diseases Program, Genetic Health, Subiaco, WA, Australia.
Gareth BaynamWestern Australian Register of Developmental Anomalies, King Edward Memorial Hospital, Subiaco, WA, Australia.
Timo Lassmann *Translational Genetics, Precision Health, The Kids Research Institute Australia, Centre for Child Health Research, Perth Children's Hospital, The University of Western Australia, Nedlands, WA, 6009, Australia.
Vanessa S Fear *Translational Genetics, Precision Health, The Kids Research Institute Australia, Centre for Child Health Research, Perth Children's Hospital, The University of Western Australia, Nedlands, WA, 6009, Australia. vanessa.fear@thekids.org.au.

Funding

Feilman Foundation LassmannMcCusker Charitable Foundation Telethon 7 Ball, Gift of Giving, 2020.National Health and Medical Research Council APP2004282Stan Perron Charitable Foundation Perron PeopleStan Perron Charitable Foundation Perron Programs and Partnership, 2025Wellcome TrustWesfarmers UWA-VCCRI Chair in Cardiovascular Research
6 · The paper itself

Abstract

backgroundPatients with congenital heart disease are identified in 1% of live births. Improved surgical intervention means many patients now survive to adulthood, the corollary of which is increased mortality in the over-65-year-old congenital heart disease (CHD) population. In the clinic, genetic sequencing increasingly identifies novel genetic variants in genes related to CHD. Traditional assays for interpreting novel genetic variants are often limited by gene-specificity, whereas animal models are cumbersome and may not accurately reflect human disease. This study investigates CRISPR gene editing in induced pluripotent stem cells and cardiomyocyte-directed differentiation as a human disease model to investigate novel genetic variants identified in association with CHD. METHODS AND

resultsWe identified a GATA4 p.Arg284His genetic variant in a paediatric patient. This genetic variant was introduced into induced pluripotent stem cells (iPSCs) using CRISPR gene editing with homology-directed-repair. GATA4 genetic variant and isogenic control iPSCs were selected and differentiated into cardiomyocytes. Expression of the GATA4 p.Arg284His variant resulted in altered calcium transients, indicative of CHD and consistent with the patient's clinical phenotype. Transcriptomics revealed cellular pathway changes in cardiac development, calcium handling, and energy metabolism that contribute to disease aetiology, mechanism and identification of potential treatments.

conclusionDirected differentiation of iPSCs harbouring the GATA4 p.Arg284His genetic variant recapitulated the CHD phenotype, indicated disease mechanisms, and pointed to potential sites for targeting with therapy. The study highlights the utility of transcriptomics for the functional interpretation of cardiac genetic variants and is an exemplar for precision medicine approaches for the investigation of CHD.

Indexed as

GATA4 Transcription FactorGenetic VariationHeart Defects, CongenitalPrecision MedicineCell DifferentiationChildCRISPR-Cas SystemsFemaleGene EditingHumansInduced Pluripotent Stem CellsMaleMyocytes, CardiacGATA4 protein, humanGATA4 Transcription FactorCardiac disease modellingCongenital heart diseaseCRISPR gene editingGATA4Induced pluripotent stem cells

Identifiers

PMID41484984
PMCPMC12866568

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