Exclusion of lumican and fibromodulin as candidate genes in MYP3linked high grade myopia

[摘要] Purpose: The proteoglycans lumican and fibromodulin regulatecollagen fibril assembly and show expression in ocular tissues. A recentmouse knockout study implicates lumican and fibromodulin as functionalcandidate genes for high myopia. Lumican maps within the chromosome12q21-q23 autosomal dominant high grade myopia-3 (MYP3) interval, andfibromodulin maps to chromosome 1q32. We screened individuals forlumican and fibromodulin sequence alterations from the original MYP3family, and from a second high grade myopia pedigree that showedsuggestive linkage to both the MYP3 interval and to chromosome 1q32.Methods: A total of 10 affected (average spherical refractive errorwas -16.13 D) and 5 unaffected individuals from the 2 families werescreened by direct DNA sequencing. Six primer pairs spanning intron-exonboundaries and coding regions were designed for the 3-exon 1804 basepair (bp) lumican gene. Two primer pairs for the 2-exon 2863 bpfibromodulin gene were designed. Polymerase chain reaction products weresequenced and analyzed using standard fluorescent methods. Sequenceswere quality scored and aligned for polymorphic analysis.Results: Direct DNA sequencing of lumican amplicons yielded theexpected sequence with no evidence of polymorphism or pathologicmutation. Sequencing of fibromodulin amplicons revealed 6 polymorphisms,1 of which was novel. One polymorphism was a silent mutation, and fivewere in the 3' untranslated region. No polymorphism segregated with highmyopia.Conclusions: Although null and double null Lum and Fmodmouse models have been developed for high myopia, our human cohort didnot show affected status association with these genes. Sequencing of thehuman lumican and fibromodulin genes has excluded them as candidategenes for MYP3 associated high grade myopia.

[学科分类] 生物化学/生物物理