Flow chart of the two patient groups for establishment of a spontaneous PMVSD closure prediction scoring system.

<p>(VSD, ventricular septal defect; CHF, congestive heart failure).</p

Baseline characteristics (categorical variables) of 1873 patients in the derivation cohort.

<p>Baseline characteristics (categorical variables) of 1873 patients in the derivation cohort.</p

Plots show SC probabilities occurring within 1 year(□) and 3 years(○) among PMVSD patients in the derivative cohort, plotted against the scoring system.

<p>The LOESS fit lines (the solid line for 1-year and the dashed line for 3-year) using 50% fit plots show the trend of SC probability against the score. (SC, spontaneous closure).</p

Baseline characteristics (continuous variables) of 1873 patients in the derivation cohort.

<p>Baseline characteristics (continuous variables) of 1873 patients in the derivation cohort.</p

Number of patients with different follow up periods in derivation and validation cohort.

<p>Number of patients with different follow up periods in derivation and validation cohort.</p

Results of multivariate Cox regression analysis in the derivation cohort.

<p>Results of multivariate Cox regression analysis in the derivation cohort.</p

Probability of SC associated with each score.

<p>Probability of SC associated with each score.</p

Scoring system for prediction of spontaneous PMVSD closure.

<p>Scoring system for prediction of spontaneous PMVSD closure.</p

Comparison among PMVSD patients of high probability(△), intermediate probably(○) and low probability(□) occurring SC by Kaplan-Meier's method.

<p>A: Probability of defect remaining open in the deviation cohort (p<0.001). B: Probability of defect remaining open in the validation cohort (p<0.001).</p

A Novel Missense Mutation of GATA4 in a Chinese Family with Congenital Heart Disease

<div><p>Background</p><p>Congenital heart disease (CHD) is the most prevalent type of birth defect in human, with high morbidity in infant. Several genes essential for heart development have been identified. GATA4 is a pivotal transcription factor that can regulate the cardiac development. Many GATA4 mutations have been identified in patients with different types of CHD.</p><p>Aims</p><p>In this study, the NKX2-5, HAND1 and GATA4 coding regions were sequenced in a family spanning three generations in which seven patients had CHD. Disease-causing potential variation in this family was evaluated by bioinformatics programs and the transcriptional activity of mutant protein was analyzed by the dual luciferase reporter assay.</p><p>Results</p><p>A novel GATA4 mutation, c.C931T (p.R311W), was identified and co-segregated with the affected patients in this family. The bioinformatics programs predicted this heterozygous mutation to be deleterious and the cross-species alignment of GATA4 sequences showed that the mutation occurred within a highly conserved amino acid. Even though it resided in the nuclear localization signal domain, the mutant protein didn’t alter its intracellular distribution. Nevertheless, further luciferase reporter assay demonstrated that the p.R311W mutation reduced the ability of GATA4 to activate its downstream target gene.</p><p>Conclusions</p><p>Our study identified a novel mutation in GATA4 that likely contributed to the CHD in this family. This finding expanded the spectrum of GATA4 mutations and underscored the pathogenic correlation between GATA4 mutations and CHD.</p></div