title: Sequence variations of NKX2-5 and HAND1 genes in patients with atrial isomerism.
abstract: OBJECTIVE
  Atrial isomerism is a congenital disorder, which is characterized by lateralization defects in normally asymmetrical developing organs like the heart. Atrial isomerism is supposed to be caused by molecular defects during early development. The NKX2-5 is a cardiac specific transcription factor, which initiates and regulates downstream transcriptional cascades of cardiogenesis. The HAND1 is another transcription factor expressed in the heart, and it is characterized by an asymmetrical pattern of expression. In this study, we aimed to test whether mutations in NKX2-5 and HAND1 genes play a role in the etiology of atrial isomerism.
  
  
  METHODS
  This case-control study consisted of 70 patients who underwent surgical treatment for congenital heart defects including atrial isomerism, 80 healthy subjects (HAND1 gene) and 40 healthy subjects (NKX2-5 gene). All exons and exon-intron boundaries of NKX2-5 and HAND1 genes were analyzed by SSCP, and suspected samples were sequenced for mutation analysis. Digestion with appropriate restriction enzymes was performed for analysis of known mutations and polymorphisms. The frequencies of the alleles and the genotypes were compared among patient and control groups using the Chi-square and the Fisher tests when appropriate.
  
  
  RESULTS
  In intronic region of HAND1 gene, we identified a C>G substitution both in patients and controls. Frequency of mutant allele (11, 42%) was found higher (p=0.046) in patient group than that of the control group (2.5%). Association between atrial isomerism and genotypes with mutant allele was found borderline significant (p=0.054). In NKX2-5 gene, we identified heterozygous Q170X (Gln170ter) mutation in one patient. We did not found any correlation between defined sequence variations and clinical properties of the patients.
  
  
  CONCLUSIONS
  Our results suggest that mutations or sequence variations in HAND1 or NKX2-5 genes may play role in etiology or pathogenesis of atrial isomerism.
authors.affiliation: Department of Cardiovascular Surgery, İstanbul University Cardiology Institute, İstanbul, Turkey. hatemi@superonline.com
authors.forename: Ali Can
authors.initials: AC
authors.lastname: Hatemi
authors.forename: Cağrı
authors.initials: C
authors.lastname: Güleç
authors.forename: Naci
authors.initials: N
authors.lastname: Cine
authors.forename: Burçak
authors.initials: B
authors.lastname: Vural
authors.forename: Ozden
authors.initials: O
authors.lastname: Hatırnaz
authors.forename: Müge
authors.initials: M
authors.lastname: Sayitoğlu
authors.forename: Funda
authors.initials: F
authors.lastname: Oztunç
authors.forename: Levent
authors.initials: L
authors.lastname: Saltık
authors.forename: Erhan
authors.initials: E
authors.lastname: Kansız
authors.forename: Nihan
authors.initials: N
authors.lastname: Erginel Ünaltuna
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D016022:Case-Control Studies; D017931:DNA Primers; D005260:Female; D006325:Heart Atria / Q000002:abnormalities*; D006330:Heart Defects, Congenital / Q000235:genetics*; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D017931:DNA Primers; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; D014157:Transcription Factors; C095552:NKX2-5 protein, human; C097341:helix-loop-helix protein, eHAND