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

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.

Variant c.2262A>C in DOCK9 Leads to Exon Skipping in Keratoconus Family.

Purpose: Keratoconus (KTCN) is a degenerative disorder of the eye that is characterized by a conical shape and thinning of the cornea, resulting in impaired visual function. Previously, we identified heterozygous single base-pair substitutions in DOCK9, IPO5, and STK24, showing concurrent 100% segregation with the affected phenotype in an Ecuadorian family. As the pathogenic consequences of these variants were not obvious, we performed in vitro splicing analyses to determine their functional significance.

Substitution at IL1RN and deletion at SLC4A11 segregating with phenotype in familial keratoconus.

Purpose: Keratoconus (KTCN) is a thinning and anterior protrusion of the cornea that results in altered refractive powers and loss of visual acuity. Despite numerous studies, the reasons for development and progression of KTCN remain unknown. Genetic studies have led to identification of several loci linked with KTCN, including a locus in one multigenerational Ecuadorian family.

Deletions and duplications of developmental pathway genes in 5q31 contribute to abnormal phenotypes.

Although copy number changes of 5q31 have been rarely reported, deletions have been associated with some common characteristics, such as short stature, failure to thrive, developmental delay (DD)/intellectual disability (ID), club feet, dislocated hips, and dysmorphic features. We report on three individuals with deletions and two individuals with duplications at 5q31, ranging from 3.6 Mb to 8.

Sequence variants in COL4A1 and COL4A2 genes in Ecuadorian families with keratoconus.

Purpose: Keratoconus (KTCN) is a non-inflammatory, usually bilateral disorder of the eye which results in the conical shape and the progressive thinning of the cornea. Several studies have suggested that genetic factors play a role in the etiology of the disease. Several loci were previously described as possible candidate regions for familial KTCN; however, no causative mutations in any genes have been identified for any of these loci.

Localization of a gene for keratoconus to a 5.6-Mb interval on 13q32.

Purpose: Keratoconus (KTCN) is a noninflammatory thinning and anterior protrusion of the cornea that results in steepening and distortion of the cornea, altered refractive powers, and reduced visual acuity. Several loci responsible for a familial form of KTCN have been mapped, however; no mutations in any genes have been identified for any of these loci. There is also evidence that VSX1 and SOD1 may be involved in the etiology of KTCN.