Familial Keratoconus in an Ecuadorian Population

Abstract

Purpose:: Keratoconus (KC) is a non-inflammatory thinning and anterior protrusion of the cornea that results in steepening and distortion of the cornea, altered refractive powers, and altered visual acuity. Although both genetic and non-genetic factors have been associated with KC, its molecular basis is still elusive. We identified an Ecuadorian cohort in which KC without other ocular or systemic features is transmitted as an autosomal dominant trait with incomplete penetrance. Here we present the results of linkage analyses and sequencing in Ecuadorian families.

Methods:: To date, we have examined, collected blood, and purified DNA from 181 individuals from 25 multiplex families with KC. Subjects were diagnosed clinically with KC by slit lamp examination and corneal topography. We excluded previously assigned KC loci on chromosomes 3, 15, 16, and 20 by linkage analysis. Additionally, the coding exons of VSX1 and SOD1 in affected individuals from the Ecuadorian families and ethnically matched control individuals were sequenced. We performed genome wide screen with fluorescent markers with an average spacing of 5 cM spanning all chromosomes.

Results:: Keratoconus in Ecuadorian families is not linked to any of the previously defined KC loci. We excluded VSX1 as a candidate for KC in this population. SOD1 sequencing analysis is in progress.

Conclusions:: Gene for keratoconus in Ecuadorian families has not been yet identified. Further genotyping will be performed.

Keywords: gene mapping • keratoconus • linkage analysis