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GATA4 mutations in 357 unrelated patients with congenital heart malformation

  • Tanya Butler
  • , Giorgia Esposito
  • , Gillian Blue
  • , Andrew Cole
  • , Mauro W Da Costa
  • , Leigh Waddell
  • , Gina Walizada
  • , Gary Sholler
  • , Edwin Kirk
  • , Michael Feneley
  • , Richard Harvey
  • , David Winlaw

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Congenital heart disease (CHD) represents one of the most common birth defects, but the genetic causes remain largely unknown. Mutations in GATA4, encoding a zinc finger transcription factor with a pivotal role in heart development, have been associated with CHD in several familial cases and a small subset of sporadic patients. To estimate the pathogenetic role of GATA4 in CHD, we screened for mutations in 357 unrelated patients with different congenital heart malformations. In addition to nine synonymous changes, we identified two known (A411V and D425N) and two novel putative mutations (G69D and P163R) in five patients with atrial or ventricular septal defects that were not seen in control subjects. The four mutations did not show altered GATA4 transcriptional activity in synergy with the transcription factors NKX2-5 and TBX20. Our data expand the spectrum of mutations associated with cardiac septal defects but do not support GATA4 mutations as a common cause of CHD.
Original languageEnglish
Pages (from-to)797 - 802
Number of pages6
JournalGenetic Testing and Molecular Biomarkers
Volume14
Issue number6
DOIs
Publication statusPublished - 2010
Externally publishedYes

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