Congenital heart defects (CHDs) occur in nearly 1% of all live births and are the major cause of infant mortality and morbidity. In addition, about 3 per every 1000 live births will require some intervention during the first year of life.1 Despite its clinical importance, the underlying genetic etiology of most CHD remains unknown. Previous studies succeeded in revealing genetic causes of some syndromic or familial CHD, however, there are limited numbers of such cases, and it is still difficult to approach the etiology of the majority of CHD, that manifest non-syndromic and non-familial phenotype, because of their multi-factorial nature.

In this issue, Lin et al. report on a novel mutation of a gene encoding a transcription factor, GATA6, as a possible cause of CHD.2 The authors screened 270 individuals with non-syndromic CHD for the GATA6 gene by direct sequencing, and identified a missense mutation (S184N) in three individuals, one with tetralogy of Fallot and the others with atrial septal defect. Although the incomplete penetrance of the phenotype by this mutation was observed, the mutation was not found in 500 ethnically matched healthy controls. And their subsequent biological analysis revealed the decreased transcriptional activity of GATA6 with the S184N mutation for the gene regulation of several important cardiac factors, suggesting that the GATA6 S184N mutation may have an important role in the pathogenesis of CHD.

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