Evaluation of small leucine–rich proteoglycans located on chromosome 12q21 in families with juvenile–onset myopia.

Abstract

Abstract: : Purpose:Juvenile–onset myopia of moderate amounts may be inherited as a complex trait involving both genetic and environmental factors. Decorin, lumican and keratocan are small leucine–rich proteoglycans (SLRP) that may participate in the development of myopia, and in alterations of the sclera and cornea that may be associated with myopia. The genes encoding these proteins are clustered with a fourth SLRP, DSPG3, on chromosome 12q21, in a region that is contained within the linkage interval for one form of inherited myopia. The purpose of this study is to determine if alterations of the SLRP gene cluster on 12q21 contribute to juvenile–onset myopia. Methods:As part of an ongoing study, the Children’s Vision Laboratory of the New England College of Optometry has tracked the refractive errors and visual function of approximately 400 subjects. At present 75 myopic subjects return for annual visits. From this population, 43 pedigrees affected by juvenile–onset myopia were identified for these studies. DNA prepared from blood samples or by the ‘swish and spit’ method have been collected from 54 individuals (31 males, 23 females) affected by juvenile–onset myopia for the initial evaluation of the selected SLRPs. The mean myopia was –4.46D (range from –0.75 to –11.50D). All the exons and flanking intron sequences for each of the four SLRP genes were amplified and sequenced using ABI chemistries and an ABI 3100 automated sequencer. Results:In this population, 17 DNA sequence variants were found within the exons and flanking introns of the four SLRP genes evaluated in this study, including 2 cSNPs, 2 deletions and one tetranucleotide repeat. The polymorphic sites are distributed throughout the 1.5 megabase region: 5 located within the DSPG3 gene (89.8 mB), 6 within the keratocan gene (89.9 mB), 3 within the lumican gene (90.0 mB), and 3 within the decorin gene (90.1 mB). Conclusions:Small leucine–rich repeat proteins are excellent candidates for genetic factors that may contribute to juvenile–onset myopia. This study has identified 17 polymorphic sites distributed throughout the genomic region containing four SLRPs including the keratocan, decorin, and lumican genes that are highly expressed in the cornea and sclera. These polymorphisms will be used to perform single–marker tests, as well as a variety of haplotype analyses to identify susceptibility alleles that may be involved in juvenile–onset myopia.

Keywords: myopia • genetics • gene screening