Key result
TBX20 mutations link to familial AF and reduce transactivation of the KCNH2 gene.
Why the study?
Inherited determinants play crucial roles in AF, but due to conspicuous genetic heterogeneity, the underlying inherited defects remain largely indefinite.
The discovery of TBX20 as a novel AF-causative gene provides new insights into the genetic mechanisms underlying atrial fibrillation.
Atrial fibrillation (AF), the most prevalent type of sustained cardiac dysrhythmia globally, confers strikingly enhanced risks for cognitive dysfunction, stroke, chronic cardiac failure, and sudden cardiovascular demise. Aggregating studies underscore the crucial roles of inherited determinants in the occurrence and perpetuation of AF. However, due to conspicuous genetic heterogeneity, the inherited defects accounting for AF remain largely indefinite. Here, via the whole-genome genotyping with genetic markers and linkage assay in a family suffering AF, a new AF-causative locus was located at human chromosome 7p14.2-p14.3, a ~4.89-cM (~4.43-Mb) interval between the markers D7S526 and D7S2250. Exome-wide sequencing assay unveiled that at the defined locus, solely the mutation in the TBX20 gene, NM_001077653.2: c.695A>G; p.(His232Arg), co-segregated with AF in the family. Additionally, Sanger sequencing assay of TBX20 in another family suffering AF uncovered a novel mutation, NM_001077653.2: c.862G>C; p.(Asp288His). Neither of the two mutations was observed in 600 unrelated control individuals. Functional investigations demonstrated that the two mutations both significantly reduced the transactivation of the target gene KCNH2 (a well-established AF-causing gene) and the ability to bind the promoter of KCNH2, while without effect on the nuclear distribution of TBX20. Conclusively, these findings reveal a new AF-causative locus at human chromosome 7p14.2-p14.3 and strongly indicate TBX20 as a novel AF-causative gene, shedding light on the mechanism underlying AF and suggesting clinical significance for allele-specific treatment of AF patients.
No takes yet. Share an insight, caveat, or question.
Li et al. (2023) studied Atrial fibrillation. TBX20 gene mutations vs. Unrelated control individuals was evaluated on Co-segregation with AF and functional effect on KCNH2 transactivation. Mutations in the TBX20 gene were identified in families with atrial fibrillation and shown to significantly reduce transactivation of the target gene KCNH2.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: