Novel TBX20 Variations Susceptible to Sporadic Atrial Fibrillation

Figures

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  Figure 1. A 12-lead electrocardiogram (ECG) recorded from the male patient suffering from sporadic atrial fibrillation (AF) carrying the TBX20 c.725C>A mutation. This representative standard ECG illustrates AF.

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  Figure 2. A truncating TBX20 mutation contributing to sporadic atrial fibrillation (AF). The sequence electropherogram traces show the heterozygous TBX20 c.725C>A mutation observed in the male case suffering from sporadic AF (Mutant), along with its wild-type control detected in a non-AF healthy subject (Wild type).

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  Figure 3. A 12-lead electrocardiogram (ECG) recorded from the female case affected with sporadic atrial fibrillation (AF) carrying the TBX20 c.826A>T mutation. This representative ECG documents AF.

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  Figure 4. A nonsense TBX20 mutation predisposing to sporadic atrial fibrillation (AF). The sequence electropherogram traces show the heterozygous TBX20 c.826A>T mutation discovered in the female patient affected with sporadic AF (Mutant), alongside its wild-type control detected in a non-AF healthy individual (Wild type).

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  Figure 5. Failure of Ser242*- or Lys276*-mutant TBX20 to transactivate KCNH2. In HeLa cells cultured in vitro, dual-luciferase activity measurements revealed that both the Ser242*-mutant TBX20 (A) and the Lys276*-mutant TBX20 (B) failed to transactivate KCNH2. Here, “a” and “c” represent p < 0.0001; “b” and “d” signify p < 0.001, when compared to wild-type TBX20 (100 ng). An error bar represents SD.

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  Figure 6. Synergistic activation of NPPA between TBX20 and NKX2.5 nullified by the Ser242* or Lys276* mutation. In COS7 cells cultivated in vitro, biochemical assays with dual-reporter genes demonstrated that the synergistic activation of NPPA by TBX20 and NKX2.5 was abolished by the Ser242* mutation (A) or the Lys276* mutation (B). Here, “e”, “f”, and “g” indicate p < 0.001; “h” denotes p < 0.005, in comparison with the corresponding wild-type counterparts. An error bar represents SD.