Abstract
INTRODUCTION: Congenital heart disease (CHD) comprises a wide spectrum of structural defects. However, the etiology of a large proportion of CHDs remains undefined. Among the genetic causes, 22q11.2 deletion syndrome is the condition which most stands out. This association is related to many cardiac embryonic development genes being in the chromosome 22 region, as well as being a region with a high probability of errors in gene recombination, influencing normal levels of gene expression and affecting a gene's copy number. OBJECTIVE: This study aimed to compare molecular findings using multiplex ligation-dependent probe amplification assay in patients presenting CHD with a previous fluorescence in situ hybridization (FISH) diagnosis of 22q11.2DS versus patients without known genetic disorder. RESULTS: All patients had CHD and facial dysmorphia. Patients who had been previously diagnosed by FISH were found to have the exact same deletion size, low-copy-number repeat sequences and genes involved. GATA4 when deleted or duplicated in different exons (1 and 6) showed distinct congenital heart defect phenotypes. Patients who did not have their diagnosis defined by FISH showed different molecular results, ranging from normal findings to alterations in the GATA and NXK2 genes. CONCLUSION: Molecular diversity in cardiac malformations is a reality and a great challenge since genotype-phenotype correlation is hindered. Therefore, new insights on that matter should be considered: 22q11.2 deletion syndrome should only be linked to the chromosome 22 region or is there a phenotype variability to be looked at that involves a broader genomic environment?