Study Suggests Genetic Mutation May Be Linked To High Myopia


This study suggests that a mutation in a gene that controls copper metabolism in parts of the eye may be linked to high myopia at least in families predisposed to the condition. Thanks to Kraig Abe for submitting this.


Medscape Medical News
Mutations Identified in High-Grade Myopia
Ricki Lewis, PhDMay 09, 2013

Mutations in a gene that controls copper metabolism in parts of the eye are linked to the severe, high-grade form of the myopia, according to results from a study published in the May 2 issue of the American Journal of Human Genetics.

High-grade myopia, with refractive error exceeding −6.00 D, runs in families and affects approximately 2% of the 33.1% of adults in the United States with myopia. It is associated with increased risk for retinal detachment, glaucoma, cataracts, and disease of the macula.

Khanh-Nhat Tran-Viet, MS, laboratory manager at the Duke Center for Human Genetics in Durham, North Carolina, and colleagues used next-generation exome sequencing of 4 members of an 11-member, 3-generation family of European descent. Nine members of the family have autosomal-dominant, nonsyndromic high-grade myopia, with an average spherical refractive error of −22.00 D.

The 4 sequenced exomes shared rare gene variants at 49 loci. The investigators then used Sanger-sequencing to analyze the variants in the other family members, including the remaining 5 affected individuals.

The relatives with high-grade myopia share a nonsense mutation in SCO2, a gene that encodes a cytochrome c oxidase assembly protein, which functions in the mitochondrial respiratory chain. Substitution of glutamine with a stop codon at position 53 truncates the protein, eliminating the catalytic domain.

The researchers then used polymerase chain reaction sequencing to analyze SCO2 in 140 unrelated cases and found 3 additional mutations. In contrast, the team found no similar mutations in 1000 control DNA samples from nonmyopic individuals.

The SCO2 protein normally carries copper in the mitochondria, and its malfunction enables reactive oxygen species to accumulate and damage DNA and ocular tissues. The phenotype affects the retina because of its high energy requirement. Damage to the retina, in turn, alters refractive development, the researchers write.

Follow-up studies further implicated the gene. The researchers tracked SCO2 gene expression in relevant structures that contribute to myopia and discovered decreased expression of the gene in eyes made myopic with artificial lenses in mice.