title: 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.affiliation: Universidad del Quindío, Armenia, Colombia.
authors.forename: Marleny
authors.initials: M
authors.lastname: Salazar
authors.forename: Federica
authors.initials: F
authors.lastname: Consoli
authors.forename: Victoria
authors.initials: V
authors.lastname: Villegas
authors.forename: Victor
authors.initials: V
authors.lastname: Caicedo
authors.forename: Valeria
authors.initials: V
authors.lastname: Maddaloni
authors.forename: Paola
authors.initials: P
authors.lastname: Daniele
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Caianiello
authors.forename: Sonia
authors.initials: S
authors.lastname: Pachón
authors.forename: Federico
authors.initials: F
authors.lastname: Nuñez
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Limongelli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pacileo
authors.forename: Bruno
authors.initials: B
authors.lastname: Marino
authors.forename: Jaime E
authors.initials: JE
authors.lastname: Bernal
authors.forename: Alessandro
authors.initials: A
authors.lastname: De Luca
authors.forename: Bruno
authors.initials: B
authors.lastname: Dallapiccola
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D005629:Frozen Sections; D050991:GATA4 Transcription Factor / Q000235:genetics*; D006343:Heart Septal Defects / Q000235:genetics*; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D014157:Transcription Factors / Q000235:genetics*; D055815:Young Adult
chemical_list: D050991:GATA4 Transcription Factor; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; C095552:NKX2-5 protein, human; D014157:Transcription Factors