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.

Determination of the Population Allelic Frequency of the Variants of the MPS Complex in Southwestern Colombia

Abstract Mucopolysaccharidoses are lysosomal storage diseases characterized by the excessive accumulation of glycosaminoglycan sulfate in organs and tissues. To determine the population allelic frequency of the MPS complex variants in a population without clinical and molecular diagnosis of MPS. An observational descriptive study was carried out where the allelic frequency of variants presents in the IDUA, IDS, SGSH, NAGLU, HGSNAT, GNS, GALNS, GLB1, ARSB, GUSB, HYAL1 genes was determined by means of the sequencing of 320 exomes from patients without a clinical diagnosis of MPS; the results were tabulated, and allelic frequency formulas were used to determine the values associated with each of the genes. 509 alleles associated with the MPS complex were reported, of which 262 have not been previously reported. Genes with the most frequent allelic presence were IDUA, GLB1 and GALNS, involved in MPS I and MPS IV A / B. The total frequencies ranged between 0.00393 (2 alleles) and 0.47937 (248 alleles). These studies make it possible to determine polymorphisms that circulate in the country, present in patients not affected with MPS, allowing to expand the knowledge about the characteristics of the alleles that are present in affected patients.

Otorhinolaryngological Findings in Patients from Southwestern Colombia with Clinical, Enzymatic and Molecular Diagnosis of Mucopolysaccharidosis II, IV-A and VI

ABSTRACT Mucopolysaccharidosis is characterized by excessive accumulation of glycosaminoglycan sulfate in organs and tissues. Otorhinolaryngological and upper respiratory tract pathologies are among the earliest clinical manifestations. We realized a retrospective study of clinical and otorhinolaryngologic findings of 35 patients diagnosed with MPS type II, IV-A and VI of the Colombian southwest. As a result, we found that 64% of the patients evaluated had hearing loss, 11.3% had hypertrophy of the tonsils,17.10% short neck and macroglossia. Additionally, 47.8% of the patients presented otitis media. 20% received treatment with hearing aids. no patient reported otosclerosis or tinittus. In patients with different types of MPS, there is a high frequency and progressive tendency to suffer audiological losses and recurrent infections, so it is important an opportune diagnosis, permanent monitoring and adequate therapy to avoid the repercussion of the pathology in the quality of life of patients.