Affiliations: Mendel Laboratory, Casa Sollievo della Sofferenza
Hospital, IRCCS, San Giovanni Rotondo, Rome, Italy | MRC Holland, Amsterdam, The Netherlands | Bambino Gesù Children Hospital, IRCCS, Rome,
Italy | Division of Pediatric Cardiology, Department of
Pediatrics, "Sapienza" University, Rome, Italy
Note: [] Corresponding author: A. De Luca, Istituto CSS-Mendel, Viale
Regina Margherita 261, 00198, Roma, Italia. Tel.: +39 06 4416 0533; Fax: +39 06
4416 0548; E-mail: a.deluca@css-mendel.it
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.
