title: R25C mutation in the NKX2.5 gene in Italian patients affected with non-syndromic and syndromic congenital heart disease.
abstract: OBJECTIVE
  Heterozygous mutations in the transcription factor Nkx2.5 indicate a genetic cause for congenital heart diseases (CHDs) in human beings. The present study aimed to assess the prevalence of NKX2.5 mutations in Italian patients with sporadic non-syndromic and syndromic CHD, as well as to appraise any genotype-phenotype correlations.
  
  
  METHODS
  One hundred Italian patients affected with CHD (90 had sporadic non-syndromic CHD and 10 had syndromic CHD) were screened for NKX2.5 mutations. The coding region and flanking regions involved in gene splicing of the CSX/NKX2.5 gene were amplified from genomic DNA by PCR, and mutational analysis was performed using denaturing high performance liquid chromatography and DNA sequencing.
  
  
  RESULTS
  One previously reported NKX2.5 mutation (c.73C>T, p.R25C) was identified in two of the 100 CHD patients (2%). We have detected the p.R25C alteration in a woman showing aneurysm of the membranous septum, aortic coarctation and bicuspid aortic valve, that was a different phenotype from those previously reported, and for the first time in a patient with syndromic CHD with Down's syndrome (posterior ventricular septal defect, atrial septal defect, left superior cava vein ' sinus, and patent ductus arteriosus).
  
  
  CONCLUSIONS
  Our results confirm that NKX2.5 mutations are not a common cause of CHD; furthermore, the p.R25C variation may increase susceptibility to development of CHD in patients with and without chromosomal abnormalities.
authors.affiliation: Department of Biology, University of Padua, Padua, Italy.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Beffagna
authors.forename: Antonella
authors.initials: A
authors.lastname: Cecchetto
authors.forename: Lucia
authors.initials: L
authors.lastname: Dal Bianco
authors.forename: Alessandra
authors.initials: A
authors.lastname: Lorenzon
authors.forename: Annalisa
authors.initials: A
authors.lastname: Angelini
authors.forename: Massimo
authors.initials: M
authors.lastname: Padalino
authors.forename: Vladimiro
authors.initials: V
authors.lastname: Vida
authors.forename: Shoumo
authors.initials: S
authors.lastname: Bhattacharya
authors.forename: Giovanni
authors.initials: G
authors.lastname: Stellin
authors.forename: Alessandra
authors.initials: A
authors.lastname: Rampazzo
authors.forename: Luciano
authors.initials: L
authors.lastname: Daliento
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000818:Animals; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis / Q000379:methods; D004285:Dogs; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006330:Heart Defects, Congenital / Q000235:genetics*; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D051379:Mice; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D051381:Rats; D016415:Sequence Alignment; D013577:Syndrome; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; C095552:NKX2-5 protein, human; D014157:Transcription Factors