title: NKX2.5 mutations in patients with non-syndromic congenital heart disease.
abstract: BACKGROUND
  Cardiac development is a complex and multifactorial biological process. Heterozygous mutations in the transcription factor NKX2.5 are between the first evidence of a genetic cause for congenital heart defects in human beings. In this study, we evaluated the presence and frequency of mutations in the NKX2.5 gene on 159 unrelated patients with a diverse range of non-syndromic congenital heart defects (conotruncal anomalies, septal defects, left-sided lesions, right-sided lesions, patent ductus arteriosus and Ebstein's anomaly).
  
  
  METHODS
  The coding region of the NKX2.5 locus was amplified by polymerase chain reaction and mutational analysis was performed using denaturing high performance liquid chromatography (DHPLC) and DNA sequencing.
  
  
  RESULTS
  We identified two distinct mutations in the NKX2.5 coding region among the 159 (1.26%) individuals evaluated. An Arg25Cys mutation was identified in a patient with Tetralogy of Fallot. The second mutation found was an Ala42Pro in a patient with Ebstein's anomaly.
  
  
  CONCLUSIONS
  The association of NKX2.5 mutations is present in a small percentage of patients with non-syndromic congenital heart defects and may explain only a few cases of the disease. Screening strategies considering the identification of germ-line molecular defects in congenital heart disease are still unwarranted and should consider other genes besides NKX2.5.
authors.affiliation: Laboratory of Genetics and Molecular Cardiology and Pediatric Cardiology Division, Heart Institute (InCor), Sao Paulo University Medical School, 05403-000 Sao Paulo, Brazil.
authors.forename: Luciana
authors.initials: L
authors.lastname: Gioli-Pereira
authors.forename: Alexandre Costa
authors.initials: AC
authors.lastname: Pereira
authors.forename: Sônia M
authors.initials: SM
authors.lastname: Mesquita
authors.forename: José
authors.initials: J
authors.lastname: Xavier-Neto
authors.forename: Antônio Augusto
authors.initials: AA
authors.lastname: Lopes
authors.forename: José Eduardo
authors.initials: JE
authors.lastname: Krieger
mesh_terms: D000595:Amino Acid Sequence; D004252:DNA Mutational Analysis; D004374:Ductus Arteriosus, Patent / Q000235:genetics; D004437:Ebstein Anomaly / Q000235:genetics; D006228:Hand Deformities, Congenital / Q000235:genetics*; D006343:Heart Septal Defects / Q000235:genetics; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D013771:Tetralogy of Fallot / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; C095552:NKX2-5 protein, human; D014157:Transcription Factors