Complexity of genetics in keratoconus

Purpose Mapping and genome sharing among affected individuals continue to be important for establishing a link between a genomic variant and its phenotypic consequences. In one large Ecuadorian keratoconus (KC) family a mutation and three other sequence variants were recognized, showing 100% segregation with disease phenotype in DOCK9, IPO5 and STK24 at 13q32 locus. Here we present further linkage and sequencing results of candidate KC genes identified in other Ecuadorian families. Methods Linkage analyses were performed in 3 large KC families. Next, candidate genes at indentified loci were screened by standard techniques using genomic DNA samples from these families and selected individuals from other Ecuadorian families and control Ecuadorian individuals. Coding exons and intron-exon boundaries of the genes were evaluated. Results Suggestive keratoconus loci, 2q13-q14.3, 20p13, and 5q31 were identified. Sequencing of IL1A, IL1B and IL1RN at 2q13-q14.3, SLC4A11 at 20p13, TGFBI, PITX1 and IL9 at 5q31 have been completed. Numerous SNV were identified in coding and non-coding regions. Conclusion Identified keratoconus loci and the sequence variants are specific for the studied families only. Our results indicate high complexity of genetics in familial keratoconus. Support: Polish Ministry of Science and Higher Education, Grant NN402591740 and National Science Center, Grant 2011/03/N/NZ5/01470