Search of somatic GATA4 and NKX2.5 gene mutations in sporadic septal heart defects.

Abstract

High prevalence of somatic mutations in the cardiac transcription factor genes NKX2.5 and GATA4 have been reported in the affected cardiovascular tissue of patients with isolated cardiac septal defects, suggesting a role of somatic mutations in the pathogenesis of these congenital heart defects (CHDs). However, all somatic mutations have been identified in DNA extracted from an archive of formalin-fixed cardiac tissues. In the present study, to address the hypothesis that somatic mutations are important in isolated CHDs, we analyzed the GATA4 and NKX2.5 genes in the fresh-frozen pathologic cardiac tissue specimen and corresponding non-diseased tissue obtained from a series of 62 CHD patients, including 35 patients with cardiac septal defects and 27 with other cardiac anomalies. We identified one variant and two common polymorphisms in the NKX2.5 gene, and six variants and two common polymorphisms in the GATA4 gene. All identified variants were seen in both the fresh-frozen pathologic cardiac tissue and the corresponding non-diseased tissue, which indicates that they all were constitutional variants. The present study has identified NKX2.5 and GATA4 constitutional variants in our CHD cohort, but was unable to replicate the previously published findings of high prevalence of somatically derived sequence mutations in patients with cardiac septal defects using fresh-frozen cardiac tissues rather than formalin-fixed tissues.

• Authors: Marleny Salazar, Federica Consoli, Victoria Villegas, Victor Caicedo, Valeria Maddaloni, Paola Daniele, Giuseppe Caianiello, Sonia Pachón, Federico Nuñez, Giuseppe Limongelli, Giuseppe Pacileo, Bruno Marino, Jaime E Bernal, Alessandro De Luca, Bruno Dallapiccola
• Journal: European journal of medical genetics (Eur J Med Genet) 2011 May-Jun Vol. 54 Issue 3 Pg. 306-9 ISSN: 1878-0849 [Electronic] Netherlands
• PMID: 21276881 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Chemical References

• GATA4 Transcription Factor
• Homeobox Protein Nkx-2.5
• Homeodomain Proteins
• NKX2-5 protein, human
• Transcription Factors

Topics

• Adolescent
• Child
• Child, Preschool
• Cohort Studies
• DNA Mutational Analysis
• Female
• Frozen Sections
• GATA4 Transcription Factor (genetics)
• Heart Septal Defects (genetics)
• Homeobox Protein Nkx-2.5
• Homeodomain Proteins (genetics)
• Humans
• Infant
• Infant, Newborn
• Male
• Mutation
• Mutation, Missense
• Myocardium (metabolism, pathology)
• Polymorphism, Single Nucleotide
• Transcription Factors (genetics)
• Young Adult