Update of genetic variants in the NKX2.5 gene

KOLOMENSKI, JORGE E.; FABBRO, MÓNICA C.; NADRA, ALEJANDRO D.; SIMONETTI, LEANDRO; DAIN, LILIANA; DELEA, MARISOL; BRUQUE, CARLOS D.

Mendoza

Congreso; A2B2C 10th Meeting; 2019

Asociación Argentina de Bioinformática y Biología Computacional

BACKGROUND: Congenital Heart Diseases (CHD) are anomalies in heart and great vessels structure and function that are present at birth. They encompass a broad spectrum of anomalies and are the most frequent type of congenital disease. In approximately 5% to 10% of patients, CHD can be associated to a variant in a single gene, and there are currently over 400 genes with variants associated to the occurrence of CHD.NKX2.5 is a homeobox protein that plays a key role in the formation of the early heart and in its function in the adult body. It is the first gene where a single genetic variant (GV) was found to be associated with CHD and, since then, the number of variants found to be associated to CHD has grown exponentially.In this study, we compiled, curated and structured GV data for the NKX2.5 gene from public databases and the scientific literature.RESULTS: A total of 1707 GVs were compiled from the different databases, comprising 1316 unique GVs. In addition, 171 GVs were found among 90 publications reviewed. 65 of these GVs were not present in any of the online databases. Furthermore, we included 2 novel GVs found in individuals from our cohort, for a total of 1383 GVs in the final database. A total of 467 variants had further in silico phenotype prediction studies.CONCLUSIONS: We have made a comprehensive survey of GVs for NKX2.5 and curated and compiled them. The resulting database has more information that any of the known databases for the gene and can be of use in the search for currently unknown genotype-phenotype correlations. We think that this can lead to a tool to help in genetic counseling of CHD in patients with known GVs and, in some cases, even unknown ones.