The Genetic and Environmental Factors for Keratoconus

Gordon‐Shaag, Ariela; Millodot, Michel; Shneor, Einat; Liu, Yutao

doi:10.1155/2015/795738

Cited by 295 publications

(263 citation statements)

References 242 publications

(322 reference statements)

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“…[2][3][4][5][6] Although the most common presentation of KTCN is sporadic, 5.0-27.9% of patients report a positive family history. 7 Generally, family pedigrees suggest KTCN is an autosomal dominant trait. However, other patterns of inheritance have also been described.…”

Section: Introductionmentioning

confidence: 99%

Variants in SKP1, PROB1, and IL17B genes at keratoconus 5q31.1–q35.3 susceptibility locus identified by whole-exome sequencing

et al. 2016

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Keratoconus (KTCN) is a protrusion and thinning of the cornea, resulting in impairment of visual function. The extreme genetic heterogeneity makes it difficult to discover factors unambiguously influencing the KTCN phenotype. In this study, we used whole-exome sequencing (WES) and Sanger sequencing to reduce the number of candidate genes at the 5q31.1-q35.3 locus and to prioritize other potentially relevant variants in an Ecuadorian family with KTCN. We applied WES in two affected KTCN individuals from the Ecuadorian family that showed a suggestive linkage between the KTCN phenotype and the 5q31.1-q35.3 locus. Putative variants identified by WES were further evaluated in this family using Sanger sequencing. Exome capture discovered a total of 173 rare (minor allele frequency o0.001 in control population) nonsynonymous variants in both affected individuals. Among them, 16 SNVs were selected for further evaluation. Segregation analysis revealed that variants c.475T4G in SKP1, c.671G4A in PROB1, and c.527G4A in IL17B in the 5q31.1-q35.3 linkage region, and c.850G4A in HKDC1 in the 10q22 locus completely segregated with the phenotype in the studied KTCN family. We demonstrate that a combination of various techniques significantly narrowed the studied genomic region and reduced the list of the putative exonic variants. Moreover, since this locus overlapped two other chromosomal regions previously recognized in distinct KTCN studies, our findings suggest that this 5q31.1-q35.3 locus might be linked with KTCN.

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Section: Introductionmentioning

confidence: 99%

Variants in SKP1, PROB1, and IL17B genes at keratoconus 5q31.1–q35.3 susceptibility locus identified by whole-exome sequencing

et al. 2016

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“…Environmental factors, including eye rubbing, atopy, and sun (Ultra Violet radiation) exposure have been implicated in the pathogenesis of keratoconus [19]. In some reports, coexistence of KTCN with atopy and allergy was presented [20][21][22].…”

Section: Pathogenesis Of Keratoconusmentioning

confidence: 99%

The Genetic Background of Keratoconus: A Review on Keratoconus Genes

Moschos¹,

Gazouli²,

Nitoda³

2016

J Clin Exp Ophthalmol

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Keratoconus is a chronic, bilateral, usually asymmetrical, non-inflammatory, ectatic disorder, being characterized by progressive steepening, thinning and apical scarring of the cornea. It affects approximately 1 in every 2000 individuals, but its incidence seems to be increased with the clinical use of corneal topography. Keratoconus is considered as a multifactorial disease, caused by the interaction between several genes, microRNAs and environmental factors, including eye rubbing, atopy, sun exposure, geographic location and race. Although the disease is usually sporadic, a genetic predisposition and raised incidence in familial and monozygotic twins have been described. Given that the diagnosis of the disease is based on a anterior eye assessment, the identification of certain genes could be an additional diagnostic tool. Furthermore, it may pave the way for the gene therapy of the disease.

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“…1,6 Different surgical options are currently available without clear consensus regarding what could be the best surgical approach for keratoconus. Corneal cross-linking (CXL) has been proposed in patients younger than 40 years to halt disease progression with limited evidence provided by properly conducted randomized controlled trial (RCT) 13 and requires a well-documented clinical progression or risk of progression patient.…”

mentioning

confidence: 99%