Abstract
Abstract: :
Purpose:The proteoglycans lumican and fibromodulin regulate collagen fibril assembly and show expression in ocular tissues. A recent mouse knockout study implicates lumican and fibromodulin as functional candidate genes for high myopia.1 Lumican maps within the chromosome 12q21–q23 autosomal dominant high–grade myopia–3 (MYP3) interval, and fibromodulin maps to chromosome 1q36. We screened individuals for lumican and fibromodulin sequence alterations from the original MYP3 family, and from a second pedigree that showed high–grade myopia linkage to both the MYP3 interval and to chromosome 1q36. Methods:A total of 10 affected (average spherical refractive error = –16.13 diopters) and 5 unaffected individuals from the 2 families were screened by direct DNA sequencing. Six primer pairs spanning intron–exon boundaries and coding regions were designed for the 3–exon 1729bp lumican gene. Two primer pairs for the 2–exon 2863bp fibromodulin gene were designed. Polymerase chain reaction products were sequenced and analyzed using standard fluorescent methods. Sequences were quality scored and aligned for polymorphic analysis. Results:Direct DNA sequencing of lumican amplicons yielded the expected sequence with no evidence of polymorphism or pathologic mutation. Sequencing of fibromodulin amplicons revealed 7 polymorphisms, 1 of which was novel. Two polymorphisms were silent mutations, and five were in the 3’ un–translated region. No polymorphisms segregated with high myopia. Conclusions:Although null and double–null Lum and Fmod mouse models have been developed for high myopia, our human cohort did not show affected status association with these genes. Sequencing of the human lumican and fibromodulin genes has excluded them as candidate genes for MYP3– associated high–grade myopia. Reference: 1. IOVS 2003;44:2422–2432.
Keywords: myopia • candidate gene analysis • gene screening