Title of article :
Screening for Novel LOX and SOD1 Variants in Keratoconus Patients from Brazil
Author/Authors :
Benevides Gadelha, Diego Nery Department of Medical Genetics - School of Medical Sciences - UNIFACISA - Campina Grande - Paraíba - Brazil , Barbosa Feitosa, Alex Felipe Department of Medical Genetics - School of Medical Sciences - UNIFACISA - Campina Grande - Paraíba - Brazil , da Silva, Rafaela Gomes Department of Medical Genetics - School of Medical Sciences - UNIFACISA - Campina Grande - Paraíba - Brazil , Talita Antunes, Luana Department of Medical Genetics - School of Medical Sciences - UNIFACISA - Campina Grande - Paraíba - Brazil , Cavalcanti Muniz, Matheus Department of Medical Genetics - School of Medical Sciences - UNIFACISA - Campina Grande - Paraíba - Brazil , de Oliveira, Matheus Alencar Department of Medical Genetics - School of Medical Sciences - UNIFACISA - Campina Grande - Paraíba - Brazil , Oliveira Andrade, Dáfine de Department of Medical Genetics - School of Medical Sciences - UNIFACISA - Campina Grande - Paraíba - Brazil , da Paz Silva, Nathalia Mayanna Department of Medical Genetics - School of Medical Sciences - UNIFACISA - Campina Grande - Paraíba - Brazil , Cronemberger, Sebastião Medical School - University of Minas Gerais - Belo Horizonte - Brazil , Fonseca Schamber-Reis, Bruno Luiz Department of Medical Genetics - School of Medical Sciences - UNIFACISA - Campina Grande - Paraíba - Brazil
Abstract :
Purpose: To investigate the presence of the variants of lysyl oxygenase (LOX) and superoxide dismutase 1 (SOD1) genes in Brazilian patients with advanced keratoconus.
Methods: Donor genomic DNA extracted from blood samples was screened for 5’UTR,
exonic LOX, and SOD1 variants in a subset of 26 patients presenting with advanced
keratoconus (KISA > 1000% and I–S > 2.0) by Sanger sequencing. The impact of
non-synonymous amino acid changes was evaluated by SIFT, PMUT, and PolyPhen
algorithms. The Mutation Taster tool was used to evaluate the potential impact of
formation of new donor and acceptor splice sites in the promoter region of affected
volunteers carrying sequence variants. A 7-base SOD1 deletion (IVS2 + 50del7bp)
previously associated with keratoconus was screened in 140 patients presenting
classical keratoconus by gel fragment analysis, and positive samples were sequenced
for confirmation.
Results: We found an unreported missense variant in LOX exon 6 in one heterozygous
patient, leading to substitution of proline with threonine at residue 392 (p. Thr392Pro)
of LOX protein sequence. This mutation was predicted to be potentially damaging to
LOX protein. Another LOX variant, Arg158Gln, was also detected in another patient
but predicted to be non-pathogenic. Two additional new polymorphisms in LOX 5’UTR
region (–116C > T and –58C > T) were found in two patients presenting with advanced
keratoconus and were predicted to modulate or create donor/acceptor splice sites in
LOX transcripts. Additionally, SOD1 deletion was detected in one patient presenting with
severe keratoconus, not in control samples.
Conclusion: We described three novel LOX polymorphisms identified for the first time
in Brazilian patients with advanced keratoconus, as well as a previously described SOD1 deletion strongly associated with keratoconus. A possible role of these variants in modulating transcript levels in the cornea of affected individual requires further investigation.
Keywords :
Keratoconus , Mutation , LOX , SOD1
Journal title :
Journal of Ophthalmic and Vision Research
