Evaluation of the X-linked high-grade myopia locus (MYP1) with cone dysfunction and color vision deficiencies.

Publications // Young Lab // Apr 01 2009

PubMed ID: 19098318

Author(s): Metlapally R, Michaelides M, Bulusu A, Li YJ, Schwartz M, Rosenberg T, Hunt DM, Moore AT, Züchner S, Rickman CB, Young TL. Evaluation of the X-linked high-grade myopia locus (MYP1) with cone dysfunction and color vision deficiencies. Invest Ophthalmol Vis Sci. 2009 Apr;50(4):1552-8. doi: 10.1167/iovs.08-2455. Epub 2008 Dec 20. PMID 19098318

Journal: Investigative Ophthalmology & Visual Science, Volume 50, Issue 4, Apr 2009

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.