Frequency of GBA gene variants in complex disease patients in Southwestern Colombia

Gaucher Disease (GD) is an autosomal recessive genetic disorder, caused by a deficiency of the enzyme B-glucocerebrosidase (GBA). In Colombia, despite considerable research on GD, the frequency of the GBA gene variants in the population is unknown, making it difficult to determine the risk of occurrence based on carriers. To identify the variants of the GBA gene, a transversal, descriptive, non-experimental study was carried out with the results obtained from the sequencing of the complete exome of 320 patients with complex disease, without clinical suspicion of GD. Bioinformatics software was used to analyze the clinical significance of the different variants. The population frequency of each variant was calculated, and a network of interaction of the GBA gene was developed. As a result, 41 variants associated with the GBA gene were found; 21/41 of the variants reported have a benign significance, 5/41 of the variants reported were classified as pathogenic or probably pathogenic and 7/41 of the variants reported presented uncertain significance. The gene interaction network showed close associations between GBA and genes PSAP, SCARB2, LAMP2, all of them focused on functions of vacuolar locations, lysosomal and vacuolar lumen instructions, vacuolar and lysosomal membranes. We conclude that the impact on the phenotype highly depends on the pathogenicity of the variants. In our sample, a high frequency of benign variants was found; however, pathogenic variants were detected, which should be the object of study in precision medicine associated with GD.

Automated summary

This study in Colombia aimed to identify GBA gene variants and their clinical significance. It found 41 variants associated with the GBA gene, some of which are pathogenic, while others are benign or of uncertain significance. The gene interaction network revealed close associations between GBA and other genes, mainly involving vacuolar locations and lysosomal functions.