Characterization of genomic variants associated with congenital heart disease in patients from southwestern Colombian.

Autor:	Grueso Cerón AL; Universidad del Valle, Faculty of Natural and Exact Sciences, Department of Biology, Biology Program, Cali, Valle del Cauca, Colombia., Arturo-Terranova D; Universidad del Valle, Faculty of Health, School of Basic Sciences, Postgraduate in Biomedical Sciences, Cali, Valle del Cauca, Colombia., Satizábal Soto JM; Universidad del Valle, Faculty of Health, School of Basic Sciences, Postgraduate in Biomedical Sciences, Cali, Valle del Cauca, Colombia.
Jazyk:	angličtina
Zdroj:	Heliyon [Heliyon] 2023 Dec 14; Vol. 10 (1), pp. e23678. Date of Electronic Publication: 2023 Dec 14 (Print Publication: 2024).
DOI:	10.1016/j.heliyon.2023.e23678
Abstrakt:	Congenital heart diseases correspond to errors during embryogenesis, generating structural and functional malformations. Congenital heart diseases are the most prevalent congenital malformations and are responsible for the highest infant morbidity and mortality. Among these cases, 8 % can be attributed to variants in genes associated with cardiac development. To establish the population frequency of genomic variants that cause congenital heart disease, a review of the scope of prevalent genes was carried out, complete exome sequencing results of 320 patients without suspicion of congenital heart disease were used, the exome sequencing is a technique based on DNA extraction using a Qiagen kit, with massive sequencing of Nextera TM libraries using an Illumina platform with 100X coverage, alignment with reference genome GRCh38/hg19, and analysis with the CRAVAT program; clinical characterization, significance classification, and gene interaction networks were performed. The scope analysis allowed to determine that the genes NKX2-5, TBX20, GATA4, NOTCH1, PTPN11 are the most prevalent, the variants with the highest allelic frequency were c.63A > G (0.2844), c.39T > C (0.3406), c.1132A > G (0.0406), c.1669+9T > C (0.3531) and c.854-30T > C (0.0875) respectively; 4 variants were reclassified by in silico tools, in the NKX2-5 gene c.335-311_335-303del from benign to probably pathogenic, in the NOTCH1 gene c.2354-24C > T from benign to pathogenic, and in the PTPN11 gene c.2354-24C > T and c.854-30T > C from benign to pathogenic. 17 % of intronic variants and 4.8 % of missense variants were identified. This work contributes to knowledge about the frequency with which genomic variants associated with congenital heart disease are present in the population, generating a tool for early diagnosis, early treatment, thus reducing morbidity and mortality, with a view to future universal molecular neonatal screening of congenital heart disease. Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (© 2023 The Authors. Published by Elsevier Ltd.)
Databáze:	MEDLINE
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