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, Bogot&aa...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2018-04-01
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| Series: | The Application of Clinical Genetics |
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| Online Access: | https://www.dovepress.com/determination-of-genotypic-and-clinical-characteristics-of-colombian-p-peer-reviewed-article-TACG |
| _version_ | 1811323204984111104 |
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| author | Tapiero-Rodriguez SM Acosta Guio JC Porras-Hurtado GL García N Solano M Pachajoa H Velasco HM |
| author_facet | Tapiero-Rodriguez SM Acosta Guio JC Porras-Hurtado GL García N Solano M Pachajoa H Velasco HM |
| author_sort | Tapiero-Rodriguez SM |
| collection | DOAJ |
| description | 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, mutation |
| first_indexed | 2024-04-13T13:50:55Z |
| format | Article |
| id | doaj.art-3bf4880d6a114cfda310ce4a9f1487e0 |
| institution | Directory Open Access Journal |
| issn | 1178-704X |
| language | English |
| last_indexed | 2024-04-13T13:50:55Z |
| publishDate | 2018-04-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | The Application of Clinical Genetics |
| spelling | doaj.art-3bf4880d6a114cfda310ce4a9f1487e02022-12-22T02:44:21ZengDove Medical PressThe Application of Clinical Genetics1178-704X2018-04-01Volume 11455737943Determination of genotypic and clinical characteristics of Colombian patients with mucopolysaccharidosis IVATapiero-Rodriguez SMAcosta Guio JCPorras-Hurtado GLGarcía NSolano MPachajoa HVelasco HMSandra 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, mutationhttps://www.dovepress.com/determination-of-genotypic-and-clinical-characteristics-of-colombian-p-peer-reviewed-article-TACGMucopolysaccharidosis IVAMorquio syndromeGALNSlysosomal storage disordermutation. |
| spellingShingle | Tapiero-Rodriguez SM Acosta Guio JC Porras-Hurtado GL García N Solano M Pachajoa H Velasco HM Determination of genotypic and clinical characteristics of Colombian patients with mucopolysaccharidosis IVA The Application of Clinical Genetics Mucopolysaccharidosis IVA Morquio syndrome GALNS lysosomal storage disorder mutation. |
| title | Determination of genotypic and clinical characteristics of Colombian patients with mucopolysaccharidosis IVA |
| title_full | Determination of genotypic and clinical characteristics of Colombian patients with mucopolysaccharidosis IVA |
| title_fullStr | Determination of genotypic and clinical characteristics of Colombian patients with mucopolysaccharidosis IVA |
| title_full_unstemmed | Determination of genotypic and clinical characteristics of Colombian patients with mucopolysaccharidosis IVA |
| title_short | Determination of genotypic and clinical characteristics of Colombian patients with mucopolysaccharidosis IVA |
| title_sort | determination of genotypic and clinical characteristics of colombian patients with mucopolysaccharidosis iva |
| topic | Mucopolysaccharidosis IVA Morquio syndrome GALNS lysosomal storage disorder mutation. |
| url | https://www.dovepress.com/determination-of-genotypic-and-clinical-characteristics-of-colombian-p-peer-reviewed-article-TACG |
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