Absence of Pathogenic Mutations in VSX1 and SOD1 Genes in Patients With Keratoconus

Štabuc-Šilih, Mirna; Stražišar, Mojca; Hawlina, Marko; Glavač, Damjan

doi:10.1097/ico.0b013e3181aebf7a

Cited by 56 publications

(57 citation statements)

References 18 publications

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“…In this study, 3 sequence variations were detected, all of which have been previously reported [3,4,18,29,30]. We found the H244R mutation in exon 4 of the gene; it was present in 2% of the patients and 2% of the healthy control subjects, which is concordant with the results of other studies [12,23,31,32,33,34,35,36] (table 3). The H244R variant is important as it is 100% conserved from flies to humans.…”

Section: Discussionsupporting

confidence: 81%

Study of VSX1 Mutations in Patients with Keratoconus in Southwest Iran Using PCR-Single-Strand Conformation Polymorphism/Heteroduplex Analysis and Sequencing Method

et al. 2013

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Objective: Keratoconus (KC) is an eye disorder in which the cornea is swollen, thinned and deformed. Despite extensive studies, the pathophysiological processes and genetic etiology of KC are unknown. The disease incidence is approximately 1 in 2,000, and it is the most common cause of corneal transplantation in the USA. Many genes are involved in the disease, but evidence suggests a major role for VSX1 in the etiology of KC. This study aimed to determine the frequency of mutations in exons 2, 3 and 4 of the VSX1 gene in Chaharmahal va Bakhtiari province in the southwest of Iran. Study Design: In this experimental study, mutations in 3 exons, namely exons 2, 3 and 4, of VSX1 were investigated in 50 patients with KC and 50 healthy control subjects. DNA was extracted using a standard phenol-chloroform method. PCR-single-strand conformational polymorphism/heteroduplex analysis was performed, followed by DNA sequencing to confirm the identified motility shifts. Results: H244R mutations were found in 1 patient and also in 1 healthy control subject. Furthermore, 12 polymorphisms were identified in patients with KC and 7 in healthy control subjects [rs6138482 and c.546A>G (rs12480307)]. Conclusion: Our investigation showed that KC-related VSX1 mutations were found in a very small proportion of the studied patients from Iran. Further investigations on other genes are needed to clarify their roles in KC pathogenesis.

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Section: Discussionsupporting

confidence: 81%

Study of VSX1 Mutations in Patients with Keratoconus in Southwest Iran Using PCR-Single-Strand Conformation Polymorphism/Heteroduplex Analysis and Sequencing Method

et al. 2013

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“…For example, the superoxide dismutase isoenzyme 1 encoded by SOD1 located on chromosome 21 was considered an attractive candidate gene because oxidative stress is hypothesised to have a role in the aetiology of KC 57 and there is an increased prevalence of KC in patients with Down syndrome (trisomy 21). 58 Despite the identification of an intronic deletion that segregated with KC in two small families, 58 this finding has not been replicated in additional cohorts, 59,60 and it remains to be established whether variants in this gene are associated with KC. Similarly, other studies have investigated the transcription factor visual system homeobox 1 encoded by VSX1, a gene implicated in posterior polymorphous corneal dystrophy (PPCD), because these PPCD patients have localised steepening of the anterior cornea similar to KC.…”

Section: Geneticsmentioning

confidence: 89%

The pathogenesis of keratoconus

Davidson¹,

Hayes

Hardcastle³

et al. 2013

Eye

294

200

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Keratoconus (KC) is a common degenerative condition that frequently results in visual loss with an onset typically in early adulthood. It is the single most common reason for keratoplasty in the developed world. The cause and underlying pathological mechanism are unknown, but both environmental and genetic factors are thought to contribute to the development of the disease. Various strategies have been employed to address the gap in our understanding of this complex disease, with the expectation that over time more sophisticated therapies will be developed. In this review we summarise our current knowledge of the aetiology and risk factors associated with KC.

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“…One of these mutations, Gly160Asp, was found in five affected patients with PPD and/or KTCN (one with PPD, three with KTCN and one with both abnormalities). However, to date, none of the subsequent studies, 64,65 including ours, 29 have confirmed a role of changes in either VSX1 or SOD1 gene in the KTCN phenotype.…”

Section: Discussionmentioning

confidence: 99%

Novel mutation and three other sequence variants segregating with phenotype at keratoconus 13q32 susceptibility locus

et al. 2011

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Keratoconus (KTCN), a non-inflammatory corneal disorder characterized by stromal thinning, represents a major cause of corneal transplantations. Genetic and environmental factors have a role in the etiology of this complex disease. Previously reported linkage analysis revealed that chromosomal region 13q32 is likely to contain causative gene(s) for familial KTCN. Consequently, we have chosen eight positional candidate genes in this region: MBNL1, IPO5, FARP1, RNF113B, STK24, DOCK9, ZIC5 and ZIC2, and sequenced all of them in 51 individuals from Ecuadorian KTCN families and 105 matching controls. The mutation screening identified one mutation and three sequence variants showing 100% segregation under a dominant model with KTCN phenotype in one large Ecuadorian family. These substitutions were found in three different genes: c.2262A4C (p.Gln754His) and c.720+43A4G in DOCK9; c.2377-132A4C in IPO5 and c.1053+29G4C in STK24. PolyPhen analyses predicted that c.2262A4C (Gln754His) is possibly damaging for the protein function and structure. Our results suggest that c.2262A4C (p.Gln754His) mutation in DOCK9 may contribute to the KTCN phenotype in the large KTCN-014 family.

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Absence of Pathogenic Mutations in VSX1 and SOD1 Genes in Patients With Keratoconus

Abstract: The absence of pathogenic mutations in our large number of unrelated patients with KC indicates that other genetic factors are involved in the development of this disorder.

Cited by 56 publications

References 18 publications

Study of <b><i>VSX1</i></b> Mutations in Patients with Keratoconus in Southwest Iran Using PCR-Single-Strand Conformation Polymorphism/Heteroduplex Analysis and Sequencing Method

Study of <b><i>VSX1</i></b> Mutations in Patients with Keratoconus in Southwest Iran Using PCR-Single-Strand Conformation Polymorphism/Heteroduplex Analysis and Sequencing Method

The pathogenesis of keratoconus

Novel mutation and three other sequence variants segregating with phenotype at keratoconus 13q32 susceptibility locus

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