Evaluation of the X-Linked High-Grade Myopia Locus (MYP1) with Cone Dysfunction and Color Vision Deficiencies

Abstract

Purpose X-linked high myopia with mild cone dysfunction and color vision defects has been mapped to chromosome Xq28 (MYP1 locus). CXorf2/TEX28 is a nested, intercalated gene within the red-green opsin cone pigment gene tandem array on Xq28. The authors investigated whether TEX28 gene alterations were associated with the Xq28-linked myopia phenotype. Genomic DNA from five pedigrees (with high myopia and either protanopia or deuteranopia) that mapped to Xq28 were screened for TEX28 copy number variations (CNVs) and sequence variants. Methods To examine for CNVs, ultra-high resolution array-comparative genomic hybridization (array-CGH) assays were performed comparing the subject genomic DNA with control samples (two pairs from two pedigrees). Opsin or TEX28 gene-targeted quantitative real-time gene expression assays (comparative CT method) were performed to validate the array-CGH findings. All exons of TEX28, including intron/exon boundaries, were amplified and sequenced using standard techniques. Results Array-CGH findings revealed predicted duplications in affected patient samples. Although only three copies of TEX28 were previously reported within the opsin array, quantitative real-time analysis of the TEX28 targeted assay of affected male or carrier female individuals in these pedigrees revealed either fewer (one) or more (four or five) copies than did related and control unaffected individuals. Sequence analysis of TEX28 did not reveal any variants associated with the disease status. Conclusions CNVs have been proposed to play a role in disease inheritance and susceptibility as they affect gene dosage. TEX28 gene CNVs appear to be associated with the MYP1 X-linked myopia phenotypes.

Nature and nurture: the complex genetics of myopia and refractive error

“…Connexin36 is essential in the transmission of rod-mediated visual signals in the mammalian retina (167,168). Evidence of photoreceptor-mediated susceptibility to myopia has previously been noted in rare X-linked disorders in which cone and/or rod function is disrupted (169)(170)(171)(172)(173)(174). To our knowledge, however, the association of a variant near GJD2 is the first evidence of a possible role for modulators of retinal visual signals in susceptibility to common refractive errors.…”

Neural Cell Adhesion Molecules Belonging to the Family of Leucine-Rich Repeat Proteins

“…Moreover, copy number variations of SLITRK2 have been associated with X-linked high myopia (near/shortsightedness) (Metlapally et al 2009 ), and SLITRK2 is also a potential candidate gene for development of dyslexia (Huc-Chabrolle et al 2013 ). However, all these potential relationships need to be confi rmed or deconfi rmed with further investigations.…”

A decade in search of myopia genes

“…Until recently, it remained unclear which gene was responsible for these defects, but work conducted by Metlapally et al has suggested one gene candidate: TEX28 (35). To better understand the role of the proposed gene, one has to first appreciate that the visual cone pigment (opsin) genes comprise a contiguous array in which a red (L) gene is followed by one or more copies of the green (M) gene.…”

“…Normally, there are 3 repetitive copies of TEX28 that are intercalated within and translated in the opposite sense to the opsin gene array (37). What Metlapally et al demonstrated is that in 5 high myopic pedigrees there were one fewer, or 4 or 5 copies of TEX28 (35). The phenomenon of copy number variants (CNV) has been proposed as a factor in disease inheritance and susceptibility as it affects "gene dosage," and thus could be the cause of high myopia in this X-linked locus.…”