A novel PRRX1 loss-of-function variation contributing to familial atrial fibrillation and congenital patent ductus arteriosus

Figures

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  Figure 1 -. A new PRRX1 variation predisposing to familial atrial fibrillation and congenital heart defect. (A) Pedigree structure of the family inflicted with atrial fibrillation and congenital heart disease. “+”, carriers of the PRRX1 variation; “-”, non-carriers. (B) Sequence electropherogram traces showing the heterozygous PRRX1 variation (mutant) as well as its homozygous wild-type control base (wild type). A rectangle delimits a codon comprising three nucleotides. (C) Schemas exhibiting the structural domains of the PRRX1 proteins. NH2, amino-terminus; COOH, carboxyl-terminus.

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  Figure 2 -. Failure to transactivate SHOX2 by Glu125*-mutant PRRX1. Dual-luciferase reporter assays unveiled that in cultured Hela cells overexpressing various recombinant expression plasmids, Glu125*-mutant PRRX1 (Glu125*) failed to transactivate the promoter of the SHOX2 gene, singly or together with wild-type PRRX1 (PRRX1). The symbols * and ** mean p<0.001 and p<0.005, respectively, in comparison with wild-type PRRX1 (200 ng).

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  Figure 3 -. No transcriptional activation on the promoter of ISL1 by Glu125*-mutant PRRX1. Biological measurement of the transactivation of the ISL1 promoter-driven luciferase in cultivated Hela cells expressing various expression plasmids by wild-type PRRX1 (PRRX1) or Glu125*-mutant PRRX1 (Glu125*), alone or in combination, revealed that Glu125* lost the ability to transcriptionally activate the promoter of the ISL1 gene. Here # and ## mean p<0.0001 and p<0.0005, respectively, in comparison with wild-type counterpart (100 ng).