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Published on: February 17, 2015
TBX5-p.G125R postnatally deregulates pacemaker cardiomyocyte state and function
Lieve E van der Maarel1, Otto J Mulleners1, Laura H F Stoop1
1Department of Medical Biology, Amsterdam Cardiovascular Sciences, Amsterdam Reproduction and Development, Amsterdam University Medical Centers, University of Amsterdam, the Netherlands.
Journal of Molecular and Cellular Cardiology
|July 19, 2026
Summary
A pathogenic TBX5 variant (p.G125R) causes atrial arrhythmias and sinus node dysfunction. This variant disrupts the adult sinus node transcriptome, impacting pacemaker function and leading to arrhythmias.
Area of Science:
- Cardiology
- Genetics
- Molecular Biology
Background:
- Holt-Oram syndrome is linked to TBX5 variants.
- TBX5 plays a role in heart development and function.
- Supraventricular arrhythmias and sinus node dysfunction are key concerns.
Purpose of the Study:
- Investigate the impact of the TBX5 p.G125R variant on cardiac arrhythmias.
- Explore the molecular mechanisms underlying TBX5-associated heart conditions.
- Analyze gene expression changes in the sinus node and atria.
Main Methods:
- Studied a family with atypical Holt-Oram syndrome.
- Utilized Tbx5+/G125R mouse models.
- Employed spatial transcriptomics for gene expression analysis.
Main Results:
- The TBX5 p.G125R variant causes atrial arrhythmias and sinus node dysfunction in mice.
- Transcriptional alterations in atria begin prenatally.
- Adult sinus node pacemaker cells show altered transcriptional states and electrophysiology.
Conclusions:
- TBX5 is critical for maintaining pacemaker cardiomyocyte function.
- Postnatal sinus node transcriptional changes drive arrhythmias.
- The TBX5 p.G125R variant disrupts cardiac electrophysiology and transcriptional regulation.
