Evidence for keratoconus susceptibility locus on chromosome 14: a genome-wide linkage screen using single-nucleotide polymorphism markers.

Objective: To search for genetic factors that could increase susceptibility to keratoconus.

Methods: A single-nucleotide polymorphism chip method was used to generate whole-genome data in a multiethnic panel of 6 families with 3 to 5 members affected by keratoconus. Candidate gene screening was performed by direct sequencing.

Results: Linkage analysis results were strongest for a locus on chromosome 14q24.3. This region contains a relatively small number of genes of potential interest, including VSX2, a homeobox gene known to be involved in eye development and implicated in a spectrum of ocular disorders. However, sequencing the coding region of VSX2 did not reveal a sequence variant segregating with disease in any of the families described.

Conclusion: To our knowledge, this is the first report of linkage for keratoconus to 14q24.3 and the region is likely to harbor important inheritable genetic factors that may affect susceptibility to keratoconus.

Clinical Relevance: Further genetic research is needed to identify the genes responsible for keratoconus. This knowledge will aid in understanding the molecular pathophysiology of this condition and may lead to improved treatment strategies.