Mutation Altering the miR-184 Seed Region Causes Familial Keratoconus with Cataract

作者：Hughes Anne E^*; Bradley Declan T; Campbell Malcolm; Lechner Judith; Dash Durga P; Simpson David A; Willoughby Colin E

来源：American Journal of Human Genetics, 2011, 89(5): 628-633.

DOI：10.1016/j.ajhg.2011.09.014

MicroRNAs (miRNAs) bind to complementary sequences within the 3' untranslated region (UTR) of mRNAs from hundreds of target genes, leading either to mRNA degradation or suppression of translation. We found that a mutation in the seed region of miR-184 (MIR184) is responsible for familial severe keratoconus combined with early-onset anterior polar cataract by deep sequencing of a linkage region known to contain the mutation. The mutant form fails to compete with miR-205 (MIR205) for overlapping target sites on the 3' UTRs of INPPL1 and ITGB4. Although these target genes and miR-205 are expressed widely, the phenotype is restricted to the cornea and lens because of the very high expression of miR-184 in these tissues. Our finding highlights the tissue specificity of a gene network regulated by a miRNA. Awareness of the important function of miRNAs could aid identification of susceptibility genes and new therapeutic targets for treatment of both rare and common diseases.

• 出版日期2011-11-11