Analysis of VSX1 variations in Brazilian subjects with keratoconus.
Purpose: To screen visual system homeobox 1 (VSX1) gene in Brazilian subjects affected with keratoconus (KCN). Methods: Seventy-three patients with KCN and 106 healthy controls were enrolled in this study. Patients were diagnosed with KCN based on eye examination and corneal topographic features acc...
| Publicado en: | Journal of Ophthalmic & Vision Research Vol. 13; no. 3; pp. 266 - 274 |
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| Autores principales: | , , , , , , , |
| Formato: | pictorial research tables/charts Journal Article |
| Publicado: |
Knowledge E DMCC
Jul-Sep2018
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=130820173&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 130820173 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 20082010 AY5S jtl: Journal of Ophthalmic & Vision Research issn: 20082010 maglogo: N pubinfo: dt: Jul-Sep2018 vid: 13 iid: 3 pid: 35682 pub: Knowledge E DMCC artinfo: ui: 130820173 130820173 130820173 10.4103/jovr.jovr_116_17 130820173 ppf: 266 ppct: 8 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Analysis of VSX1 variations in Brazilian subjects with keratoconus. aug: au: Silva, Dulceria Gadelha, Bianca Feitosa, Alex Silva, Rafaela Albuquerque, Tarsila Santos, Débora Gadelha, Diego Fonseca Schamber-Reis, Bruno affil: Department of Medical Genetics, School of Medical Sciences, UNIFACISA, Campina Grande; Federal University of Paraíba, Campina Grande, Paraíba sug: subj: Keratoconus Diagnosis Genetic Screening Polymorphism, Genetic Human Brazil Diagnosis, Eye Corneal Topography Blood Donors Amino Acids DNA Genotype Mutation Silicon Analysis Severity of Illness Adolescence Child Child, Preschool Infant Adolescent: 13-18 years Child: 6-12 years Child, Preschool: 2-5 years Infant: 1-23 months ab: Purpose: To screen visual system homeobox 1 (VSX1) gene in Brazilian subjects affected with keratoconus (KCN). Methods: Seventy-three patients with KCN and 106 healthy controls were enrolled in this study. Patients were diagnosed with KCN based on eye examination and corneal topographic features according to Rabinowitz's criteria (K > 47.2, I-S > 1.4 and KISA > 100%). DNA from blood samples was extracted from donors, and the exons and exon-intron boundaries of VSX1 were sequenced. The potential impact of the identified amino acid changes was assessed with Poly-Phen2, SIFT, and PMUT analysis tools. Genotyping was confirmed by RLFP technique, which was also applied to genotype non-affected individuals. Results: We found three non-synonymous substitutions (L68H, R131S, and D105E) in VSX1 exon 1, with L68H mutation as a novel variation in this gene. In silico analysis indicated that all variations found were predicted to be probably damaging to VSX1 structure and function. Examination of R131S and L68H variations segregating in one family suggested a strong effect of these variations in increasing disease severity in the proband, which presented bilateral KCN leading to corneal grafting before the age of sixteen. We found a novel synonymous substitution (P79P) and two previously described exonic polymorphisms, with unknown roles in VSX1 pathogenesis. Conclusion:VSX1 polymorphisms found in the Brazilian population support a genetic component in KCN pathogenesis. L68H is a novel mutation, and the phenotypic data suggest that this mutation might enhance disease severity when combined with other polymorphisms. However, further investigations are needed. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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