{"corpus_id":34037419,"paper_sha":"4b7c6c7f460fdc8c0cc84426ef78f5c1ccfc5f4a","doi":"10.1016/j.ajhg.2011.09.014","arxiv_id":null,"pmid":21996275,"pmcid":"PMC3213395","mag_id":2093992697,"dblp_id":null,"acl_id":null,"title":"Mutation altering the miR-184 seed region causes familial keratoconus with cataract.","year":2011,"publication_date":"2011-11-11","venue":"American Journal of Human Genetics","journal":{"name":"American journal of human genetics","pages":"\n          628-33\n        ","volume":"89 5"},"journal_issn":null,"journal_title":null,"publication_types":["JournalArticle"],"pubmed_pub_types":["Journal Article","Research Support, Non-U.S. Gov't"],"s2_fields_of_study":["Biology","Medicine"],"reference_count":32,"citation_count":280,"influential_citation_count":14,"is_open_access":true,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":[{"d":"3' Untranslated Regions","mj":false,"qs":[{"q":"genetics","mj":false,"ui":"Q000235"}],"ui":"D020413"},{"d":"Case-Control Studies","mj":false,"ui":"D016022"},{"d":"Cataract","mj":false,"qs":[{"q":"congenital","mj":true,"ui":"Q000151"},{"q":"genetics","mj":false,"ui":"Q000235"}],"ui":"D002386"},{"d":"Cornea","mj":false,"qs":[{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D003315"},{"d":"HeLa Cells","mj":false,"ui":"D006367"},{"d":"High-Throughput Nucleotide Sequencing","mj":false,"ui":"D059014"},{"d":"Humans","mj":false,"ui":"D006801"},{"d":"Integrin beta4","mj":false,"qs":[{"q":"genetics","mj":false,"ui":"Q000235"}],"ui":"D039663"},{"d":"Keratoconus","mj":false,"qs":[{"q":"genetics","mj":true,"ui":"Q000235"}],"ui":"D007640"},{"d":"Lens, Crystalline","mj":false,"qs":[{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D007908"},{"d":"MicroRNAs","mj":false,"qs":[{"q":"genetics","mj":true,"ui":"Q000235"}],"ui":"D035683"},{"d":"Mutation","mj":true,"ui":"D009154"},{"d":"Northern Ireland","mj":false,"ui":"D009660"},{"d":"Organ Specificity","mj":false,"qs":[{"q":"genetics","mj":true,"ui":"Q000235"}],"ui":"D009928"},{"d":"Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases","mj":false,"ui":"D000072183"},{"d":"Phosphoric Monoester Hydrolases","mj":false,"qs":[{"q":"genetics","mj":false,"ui":"Q000235"}],"ui":"D010744"},{"d":"Polymorphism, Genetic","mj":false,"ui":"D011110"},{"d":"Sequence Analysis, RNA","mj":false,"ui":"D017423"},{"d":"Sequence Homology, Nucleic Acid","mj":false,"ui":"D012689"}],"chemicals":[{"n":"3' Untranslated Regions","ui":"D020413","reg":"0"},{"n":"Integrin beta4","ui":"D039663","reg":"0"},{"n":"MicroRNAs","ui":"D035683","reg":"0"},{"n":"Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases","ui":"D000072183","reg":"EC 3.1.3.86"},{"n":"Phosphoric Monoester Hydrolases","ui":"D010744","reg":"EC 3.1.3.2"},{"n":"ITGB4 protein, human","ui":"C059834","reg":"0"},{"n":"MIRN184 microRNA, human","ui":"C534424","reg":"0"},{"n":"MIR205, human","ui":"C534425","reg":"0"},{"n":"INPPL1 protein, human","ui":"C098706","reg":"EC 3.1.3.86"}],"comments_corrections":null,"source_flags":5,"s2_open_access_pdf_url":"http://www.cell.com/article/S0002929711004046/pdf","s2_open_access_landing_url":"https://www.semanticscholar.org/paper/4b7c6c7f460fdc8c0cc84426ef78f5c1ccfc5f4a","s2_open_access_license":"publisher-specific-oa","s2_open_access_status":"BRONZE","pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"abstract":"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.","claims":[{"public_id":"cl_dbaf002776e272470d0f3a7ae00bc83b","status":"active","text":"A mutation in the seed region of miR-184 is responsible for familial severe keratoconus combined with early-onset anterior polar cataract.","confidence":0.97,"contributors":[{"id":136,"public_id":"3c2apqe3ut","public_label":"Anonymous (3c2apqe3ut)","roles":["extraction"],"url":"https://sah.borca.ai/u/3c2apqe3ut"},{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["review"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ 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cornea- and lens-restricted phenotype is attributed to very high expression of miR-184 in these tissues despite wider expression of the target genes and miR-205.","confidence":0.94,"contributors":[{"id":136,"public_id":"3c2apqe3ut","public_label":"Anonymous (3c2apqe3ut)","roles":["extraction"],"url":"https://sah.borca.ai/u/3c2apqe3ut"},{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["review"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["review"],"url":"https://sah.borca.ai/u/ezd9qvkvax"}],"url":"https://sah.borca.ai/claims/cl_5335491831c48143482b51b2caeddc47"},{"public_id":"cl_bad9c75e5648bfb41897e65c3c3a29a4","status":"active","text":"The mutant form of miR-184 fails to compete with miR-205 for overlapping target sites on the 3' UTRs of INPPL1 and ITGB4.","confidence":0.96,"contributors":[{"id":136,"public_id":"3c2apqe3ut","public_label":"Anonymous 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