Molecular Characterization of the GBA Gene in Patients from Southwest of Colombia with Gaucher Disease

Abstract

Introduction: Gaucher's disease (GD) is an autosomal-recessive lysosomal storage disorder that results from hereditary deficiency of the acid glucocerebrosidase enzyme, encoded by the GBA gene necessary for the degradation of glucosylceramide. Objective: molecularly characterize the variants found in the GBA gene present in patients from the Southwest of Colombia with GD. Material and methods: 19 patients were included in the study, clinically and enzymatically diagnosed with GD. A molecular analysis of the GBA gene was performed and the variants were subsequently searched in different population and clinical databases. A bioinformatic analysis was performed. Results:The variants in the GBA gene reported were classified into: 14/19 homozygous patients, 4/19 compound heterozygote and 1/19 heterozygous. The presence of 7 variants coding for 8 different genotypes was reported. Also the known mutations like Asn409Ser, p.Leu483Pro, p.Lys237Glu, p.Glu427Lys, and p.Arg535His were identified in these patients. The most frequent genotype was p. Asn409Ser / Asn409Ser (36%). All the variants presented a pathogenic clinical significance. Conclusion:The given study will make it possible to understand the susceptibility to GD in the population. This can help maintain the health quotient of the population through premarital counseling and therefore minimize the burden of disease among the population.

Bone manifestations in patients with Gaucher disease type 1 in southwestern Colombia

“…Additionally, with respect to molecular studies, the analysis of copy number variations (CNVs) by next-generation sequencing has reduced sensitivity and speci city when considering events (deletions or duplications) involving only one or two exons, as well as for CNVs in genes with pseudogenes and/or regions with a high degree of homology. Furthermore, this analysis did not reveal chromosomal abnormalities involving entire chromosomes (aneuploidies and polyploidy) (33).…”

“…Patients with the pathogenic variant of the GBA gene (p.Asn409Ser) are more likely to develop bone symptoms, such as bone pain, bone fractures, and osteonecrosis. The connection between this genetic variant and bone damage in GD1 patients is related to the accumulation of glucocerebroside in bone cells, which leads to dysfunction and, eventually, bone damage (33,34) .…”

“…Leu483Pro variant and bone damage lies in the accumulation of glucocerebroside in bone cells, which leads to dysfunction and eventually bone damage. The accumulation of the lipid glucocerebroside affects the normal function of bone cells and may interfere with normal bone remodeling, increasing the risk of fractures and other bone problems (33,34,35).…”