Genomic variants associated with inborn errors of lipid metabolism in southwestern Colombia.

Inborn errors of metabolism (IEM) are heritable disorders that produce failures in the metabolic pathways involved in the breakdown or storage of carbohydrates, lipids and proteins; genetic damage in the enzymes responsible for their degradation cause the accumulation of substrates and metabolites, which also affect the functioning of other proteins, energy production and generate the accumulation of other biomolecules in organs and tissues. In Colombia, there are no exact epidemiological figures of these diseases due to their underreporting. For this reason, genomic variants in genes associated with lipid IEM were searched for, identified and characterized through a cross-sectional, observational, descriptive study on the results of 320 complete exomes of the population of southwestern Colombia without clinical or paraclinical diagnosis of this group of diseases. Genomic variants were submitted to clinical, population and in-silico prediction databases and classified according to the standards of the American College of Medical Genetics and Genomics (ACMG). In addition, allele frequency was calculated and interaction networks were used for each gene. We found 262 genomic variants of which; 71 variants were benign or probably benign, 12 variants of uncertain significance (VUS), 2 pathogenic and 5 probably pathogenic in LDLR, APOE, ACADS, ACADM, CPT2 and HADHA genes. In addition, 50 intronic, 18 missense, 22 synonymous and 172 previously unreported variants were identified. The pathogenic or probably pathogenic variants were p.Thr228Asn; p.Arg171Trp; p.Asp118Gly; p.Phe352Cys; p.Ser113Leu; p.Arg176Cys; p.Arg163Cys, with p.Arg176Cys having the highest allelic frequency of 2.1%. Gene-molecule interaction networks reported relationship between genes with shared ontological functions with other genes and nearby metabolic pathways. The results described here are relevant for decision making by health authorities, focused on neonatal screening for early detection and intervention to reduce morbidity and mortality attributed to these diseases, including appropriate genetic counseling, thus approaching precision medicine.