title: miRNA mutations are not a common cause of deafness.
abstract: Mutations in miRNA genes have been implicated in hearing loss in human families and mice. It is also possible that mutations in miRNA binding sites of inner ear targets alter gene expression levels and lead to hearing loss. To investigate these possibilities we screened predicted target genes of the miR-183 miRNA cluster known to be expressed in the inner ear sensory epithelium. In one Iranian family segregating autosomal recessive non-syndromic hearing loss (ARNSHL), we identified a homozygous variant in a predicted miR-96/182 binding site in the 3'UTR of the RDX (DFNB24) gene. However, in vitro functional studies showed that this site is not a functional target for miR-96/182. We extended our study to include the miR-183 genes themselves and 24 additional predicted target genes of the miRNA-183 cluster. Screening these miRNAs and target sequences in numerous families segregating either autosomal dominant non-syndromic deafness (ADNSHL) or ARNSHL did not identify any potential deafness-causing mutations. These results suggest that mutations disrupting gene regulation by the miR-183 cluster are not a common cause of human hearing loss.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Iowa, Iowa City, Iowa 52242, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Hildebrand
authors.forename: P Dane
authors.initials: PD
authors.lastname: Witmer
authors.forename: Shunbin
authors.initials: S
authors.lastname: Xu
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Newton
authors.forename: Kimia
authors.initials: K
authors.lastname: Kahrizi
authors.forename: Hossein
authors.initials: H
authors.lastname: Najmabadi
authors.forename: David
authors.initials: D
authors.lastname: Valle
authors.forename: Richard J H
authors.initials: RJ
authors.lastname: Smith
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D003638:Deafness / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D005808:Genes, Recessive; D006720:Homozygote; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D005810:Multigene Family; D009154:Mutation; D010375:Pedigree; D012689:Sequence Homology, Nucleic Acid
chemical_list: D020413:3' Untranslated Regions; D003598:Cytoskeletal Proteins; D017931:DNA Primers; C533449:MIRN183 microRNA, human; C541492:MIRN96 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; C538984:Mirn182 microRNA, human; C071776:radixin