Genetics in Keratoconus: where are we?. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: Bykhovskaya, Yelena; Margines, Benjamin; Rabinowitz, Yaron
• Is Part Of: Eye and vision. Volume 3:Issue 1(2016)
• Page Start: 1
• Page End: 10
• Publication Date: 2016-12
• Subjects: Keratoconus -- Genetics -- Complex disease -- Genetic variation -- Linkage -- Genetic association -- Sequencing -- Corneal dystrophy -- Genotyping; Ophthalmology -- Periodicals; Vision -- Periodicals; Optometry -- Periodicals; 617.7
• DOI: 10.1186/s40662-016-0047-5
• Languages: English
• ISSNs: 2326-0254

Abstract

Abstract Keratoconus (KC) is a non-inflammatory thinning and protrusion of the cornea in which the cornea assumes a conical shape. Complex etiology of this condition at present remains an enigma. Although environmental factors have been involved in KC pathogenesis, strong underlining genetic susceptibility has been proven. The lack of consistent findings among early genetic studies suggested a heterogeneity and complex nature of the genetic contribution to the development of KC. Recently, genome-wide linkage studies (GWLS) and genome-wide association studies (GWAS) were undertaken. Next-generation sequencing (NGS)-based genomic screens are also currently being carried out. Application of these recently developed comprehensive genetic tools led to a much greater success and increased reproducibility of genetic findings in KC. Involvement of theLOX gene identified through GWLS has been confirmed in multiple cohorts of KC patients around the world. KC susceptibility region located at the 2q21.3 chromosomal region near theRAB3GAP1 gene identified through GWAS was independently replicated. Rare variants in theZNF469 gene (mutated in corneal dystrophy Brittle Cornea Syndrome) and in theTGFBI gene (mutated in multiple corneal epithelial–stromal TGFBI dystrophies) have been repeatedly identified in familial and sporadic KC patients of different ethnicities. Additional comprehensive strategies using quantitative endophenotypes have been successfully employed to bring further understanding to the genetics of KC. Additional genetic determinants including theCOL5A1 gene have been identified in the GWAS of KC-related trait central corneal thickness. These recent discoveries confirmed the importance of the endophenotype approach for studying complex genetic diseases such as KC and showed that different connective tissue disorders may have the same genetic determinants.