Determination of genotypic and clinical characteristics of Colombian patients with mucopolysaccharidosis IVA

Sandra M Tapiero-Rodriguez,1 Johanna C Acosta Guio,1 Gloria Liliana Porras-Hurtado,2 Natalia García,3 Martha Solano,4 Harry Pachajoa,5 Harvy M Velasco1 1Universidad Nacional de Colombia, Departamento de morfología, Maestría de genética humana, Bogotá, 2Family Compensation Fund of Risaralda, Pereira, 3Faculty of Medicine, Manizales University, Manizales, 4Department of Neuropediatrics, Cardioinfantil Foundation, Bogotá, 5Centro de Investigaciones en Anomalías Congénitas y Enfermedades Raras, Universidad ICESI y Fundación Valle del Lili, Cali, Colombia Background: As mucopolysaccharidosis IVA (MPS IVA) is the most frequent MPS in Colombia, this paper aims to describe its clinical and mutational characteristics in 32 diagnosed patients included in this study. Methods: Genotyping was completed by amplification and Sanger sequencing of the GALNS gene. The SWISS-model platform was used for bioinformatic analysis, and mutant proteins were generated by homology from the wild-type GALNS code 4FDI template from the Protein Data Bank (PDB) database. Docking was performed using the GalNAc6S ligand (PubChem CID: 193456) by AutoDock Vina 1.0 and visualized in PyMOL and LigPlot+. Results: Eleven variants were identified, and one new pathogenic variant was described in the heterozygous state, which is consistent with genotype c. 319 G>T or p.Ala107Ser. The pathogenic variant c.901G>T or p.Gly301Cys was the most frequent mutation with 51.6% of alleles. Docking revealed affinity energy of −5.9 Kcal/mol between wild-type GALNS and the G6S ligand. Some changes were evidenced at the intermolecular interaction level, and affinity energy for each mutant decreased. Conclusion: Clinical variables and genotypic analysis were similar to those reported for other world populations. Genotypic data showed greater allelic heterogeneity than those previously reported. Bioinformatics tools showed differences in the binding interactions of mutant proteins with the G6S ligand, in regard the wild-type GALNS. Keywords: mucopolysaccharidosis IVA, Morquio syndrome, GALNS, lysosomal storage disorder, mutatio