Analysis of chromosomal abnormalities, genomic imbalances, and sequence variants as cause of congenital heart defects

Abstract

INTRODUCTION: Congenital heart diseases (CHD) are structural anomalies of the heart and great vessels present at birth.
CHD encompass a broad spectrum of anomalies affecting around 0.6%-0.9% of all live births worldwide. In Argentina, CHD account for one-third of all birth defects. Their etiology is heterogeneous; however, family recurrence has been observed in  accordance with the influence of genetic factors. The objective of the study was to analyze the presence of chromosomal  abnormalities, genomic imbalances and/or sequence variants in a sample of children with CHD in Argentina. METHODS: A total  of 289 patients with CHD up to 16 years old were included. Karyotyping was performed for patients with other birth defects,  and genomic regions associated with CHD were studied by multiplex ligation-dependent probe amplification (MLPA) in patients  with conotruncal CHD. In selected samples, genomic imbalances and/or sequence variants were analyzed by array  comparative genomic hybridization (a-CGH) or by direct sequencing of the NKX2-5 gene, respectively. RESULTS: There were 9  patients with chromosomal abnormalities, 21 had genomic imbalances detected by MLPA and 8 by array-CGH. No pathogenic  variants were found in NKX2-5. DISCUSSION: The genetic cause was found in 13% of the analyzed cases. This work represents  the first study in patients with CHD either isolated or associated with other birth defects in Argentina.