Department of Otolaryngology-Head and Neck Surgery, University of Iowa, Iowa City, Iowa 52242, USA.
Am J Med Genet A. 2010 Mar;152A(3):646-52. doi: 10.1002/ajmg.a.33299.
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.
miRNA 基因的突变已被认为与人类和小鼠的听力损失有关。内耳靶基因的 miRNA 结合位点的突变也可能改变基因表达水平，导致听力损失。为了研究这些可能性，我们筛选了已知在内耳感觉上皮细胞中表达的 miR-183 微RNA 簇的预测靶基因。在一个伊朗家族中，常染色体隐性非综合征性听力损失（ARNSHL）呈常染色体隐性遗传，我们在 RDX（DFNB24）基因的 3'UTR 中发现了一个 miR-96/182 结合位点的纯合变异。然而，体外功能研究表明，该位点不是 miR-96/182 的功能性靶标。我们将研究扩展到包括 miR-183 基因本身以及 miRNA-183 簇的另外 24 个预测靶基因。在许多常染色体显性非综合征性耳聋（ADNSHL）或 ARNSHL 家系中筛选这些 miRNA 和靶序列，并未发现任何潜在的致聋突变。这些结果表明，miR-183 簇基因调控破坏的突变不是人类听力损失的常见原因。
