Variation in the L and M cone opsin genes as a causative factor in myopia

Abstract

Purpose: A sequence variation in the L cone opsin gene has been shown to underlie an X-linked form of cone dysfunction that presents with red-green color blindness and myopia (Bornholm Eye Disease). This raises the possibility that other forms of myopia may also be associated with changes in the L and M opsin genes. The objective of this study was to determine the extent of L and M opsin gene variation and to assess the role of such variants in the onset of myopia.

Methods: Isolated genomic DNA was obtained with informed consent from male participants recruited from three study groups, the Norfolk Island Eye Study, the Raine Eye Health Study and the Australian Inherited Retinal Disease Register. Myopia was defined as <=-3 Diopters. L and M opsin genes were amplified using long range PCR, followed by the individual amplification and sequencing of exons 2-5.

Results: Sequencing analysis revealed a number of previously unreported variants that were common to either both normal and myopic groups (8 homozygous, 18 heterozygous), or unique to myopic subjects (2 homozygous, 31 heterozygous). Five cases displayed novel haplotypes involving exons 4 and 5, but none had the BED haplotype.

Conclusions: This study re-enforces the variability within the L and M opsin array on the X chromosome, and identifies variants that may be involved in the causation of common myopia, and in the development of other disorders. Further functional analyses are required to determine the mechanism of action of such changes.

Keywords: 605 myopia • 470 color pigments and opsins • 537 gene screening