Mutation altering the miR-184 seed region causes keratoconus with cataract

Anne Hughes, Declan Bradley, Malcolm Campbell, Judith Lechner, Durga Dash, David Simpson, Colin Willoughby

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182 Citations (Scopus)
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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 may aid identification of susceptibility genes and new therapeutic targets for treatment of both rare and common diseases.
Original languageEnglish
Pages (from-to)628-633
Number of pages6
JournalThe American Journal of Human Genetics
Issue number5
Publication statusPublished - 11 Nov 2011

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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