Mutational analysis of MIR184 in sporadic keratoconus and myopia

Judith Lechner, Ha Ae Bae, Jasenka Guduric-Fuchs, Aine Rice, Gowthaman Govindarajan, Salina Siddiqui, Layal Abi Farraj, Shea Ping Yip, Keng Hung Maurice Yap, Manoranjan Das, Emmanuelle Souzeau, Doug Coster, Richard A. Mills, Richard Lindsay, Tony Phillips, Paul Mitchell, Manir Ali, Chris F. Inglehearn, Periasamy Sundaresan, Jamie E. CraigDavid A. Simpson, Kathryn P. Burdon, Colin E. Willoughby

Research output: Journal article publicationJournal articleAcademic researchpeer-review

46 Citations (Scopus)


PURPOSE. A mutation miR-184({thorn}57C>T) in the seed region of miR-184 (encoded by MIR184 [MIM*613146]) results in familial severe keratoconus combined with early-onset anterior polar cataract and endothelial dystrophy, iris hypoplasia, congenital cataract, and stromal thinning (EDICT) syndrome (MIM#614303). In order to investigate the phenotypic spectrum resulting from MIR184 mutation, MIR184 was sequenced in a keratoconus cohort of mixed ethnicity and a Chinese axial myopia cohort. METHODS. Sequencing of MIR184 was performed in 780 unrelated keratoconus patients and 96 unrelated Han southern Chinese subjects with axial myopia. Effects of identified mutations on RNA secondary structure were predicted computationally using mFold and RNAFold algorithms. MIR184 amplicons from patients harboring mutations were cloned and transfected into human embryonic kidney 293T (HEK293T) cells, and mature mutant miR184 expression was analyzed by stem-loop real-time quantitative PCR (RT-qPCR). RESULTS. Two novel heterozygous substitution mutations in MIR184 were identified in the two patients with isolated keratoconus: miR-184({thorn}8C>A) and miR-184({thorn}3A>G). Computational modeling predicted that these mutations would alter the miR-184 stem-loop stability and secondary structure. Ex vivo miR-184 expression analysis demonstrated that miR184({thorn}8C>A) almost completely repressed the expression of miR-184 (P = 0.022), and miR-184({thorn}3A>G) reduced the expression of miR-184 by approximately 40% (P = 0.002). There was no significant association of rs41280052, which lies within the stem-loop of miR184, with keratoconus. No MIR184 mutations were detected in the axial myopia cohort. CONCLUSIONS. Two novel heterozygous substitution mutations in MIR184 were identified in two patients with isolated keratoconus: miR-184({thorn}8C>A) and miR-184({thorn}3A>G). Mutations in MIR184 are a rare cause of keratoconus and were found in 2 of 780 (0.25%) cases. &copy: 2013 The Association for Research in Vision and Ophthalmology, Inc.
Original languageEnglish
Pages (from-to)5266-5272
Number of pages7
JournalInvestigative Ophthalmology and Visual Science
Issue number8
Publication statusPublished - 1 Jan 2013


  • Corneal dystrophies
  • Hereditary
  • Hsa-miR-184
  • Keratoconus
  • Mir184
  • Myopia

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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