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AIMS: 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). CONCLUSION: 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.

Original publication




Journal article


J Cardiovasc Med (Hagerstown)

Publication Date





582 - 586


Adolescent, Adult, Aged, Amino Acid Sequence, Animals, Case-Control Studies, Child, Child, Preschool, DNA Mutational Analysis, Dogs, Gene Frequency, Genetic Predisposition to Disease, Heart Defects, Congenital, Homeobox Protein Nkx-2.5, Homeodomain Proteins, Humans, Infant, Infant, Newborn, Mice, Middle Aged, Molecular Sequence Data, Mutation, Pedigree, Rats, Sequence Alignment, Syndrome, Transcription Factors