title: Multiplex ligation-dependent probe amplification analysis of GATA4 gene copy number variations in patients with isolated congenital heart disease.
abstract: GATA4 mutations are found in patients with different isolated congenital heart defects (CHDs), mostly cardiac septal defects and tetralogy of Fallot. In addition, GATA4 is supposed to be the responsible gene for the CHDs in the chromosomal 8p23 deletion syndrome, which is recognized as a malformation syndrome with clinical symptoms of facial anomalies, microcephaly, mental retardation, and congenital heart defects. Thus far, no study has been carried out to investigate the role of GATA4 copy number variations (CNVs) in non-syndromic CHDs. To explore the possible occurrence of GATA4 gene CNVs in isolated CHDs, we analyzed by multiplex ligation-dependent probe amplification (MLPA) a cohort of 161 non-syndromic patients with cardiac anomalies previously associated with GATA4 gene mutations. The patients were mutation-negative for GATA4, NKX2.5, and FOG2 genes after screening with denaturing high performance liquid chromatography. MLPA analysis revealed that normalized MLPA signals were all found within the normal range values for all exons in all patients, excluding a major contribution of GATA4 gene CNVs in CHD pathogenesis.
authors.affiliation: Casa Sollievo della Sofferenza Hospital, IRCCS, San Giovanni Rotondo, Rome, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Guida
authors.forename: Francesca
authors.initials: F
authors.lastname: Lepri
authors.forename: Raymon
authors.initials: R
authors.lastname: Vijzelaar
authors.forename: Andrea
authors.initials: A
authors.lastname: De Zorzi
authors.forename: Paolo
authors.initials: P
authors.lastname: Versacci
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Digilio
authors.forename: Bruno
authors.initials: B
authors.lastname: Marino
authors.forename: Alessandro
authors.initials: A
authors.lastname: De Luca
authors.forename: Bruno
authors.initials: B
authors.lastname: Dallapiccola
mesh_terms: D015331:Cohort Studies; D004247:DNA / Q000235:genetics; D005091:Exons / Q000235:genetics; D050991:GATA4 Transcription Factor / Q000235:genetics*; D018628:Gene Dosage; D014644:Genetic Variation / Q000235:genetics*; D006330:Heart Defects, Congenital / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D009154:Mutation / Q000235:genetics; D021141:Nucleic Acid Amplification Techniques; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction; D013577:Syndrome
chemical_list: D050991:GATA4 Transcription Factor; C484170:GATA4 protein, human; D015345:Oligonucleotide Probes; D004247:DNA