Genetics in Keratoconus: where are we?

摘要: Keratoconus (KC) is a non-inflammatory thinning and protrusion of the cornea in which assumes conical shape. Complex etiology this condition at present remains an enigma. Although environmental factors have been involved KC pathogenesis, strong underlining genetic susceptibility has proven. The lack consistent findings among early studies suggested heterogeneity complex nature contribution to development KC. Recently, genome-wide linkage (GWLS) association (GWAS) were undertaken. Next-generation sequencing (NGS)-based genomic screens are also currently being carried out. Application these recently developed comprehensive tools led much greater success increased reproducibility Involvement LOX gene identified through GWLS confirmed multiple cohorts patients around world. region located 2q21.3 chromosomal near RAB3GAP1 GWAS was independently replicated. Rare variants ZNF469 (mutated corneal dystrophy Brittle Cornea Syndrome) TGFBI epithelial–stromal dystrophies) repeatedly familial sporadic different ethnicities. Additional strategies using quantitative endophenotypes successfully employed bring further understanding genetics determinants including COL5A1 KC-related trait central thickness. These recent discoveries importance endophenotype approach for studying diseases such as showed that connective tissue disorders may same determinants.