Mutations in the seed region of human miR-96 are responsible for nonsyndromic progressive hearing loss - PubMed (original) (raw)

doi: 10.1038/ng.355. Epub 2009 Apr 12.

Silvia Modamio-Høybjør, Nick Redshaw, Matías Morín, Fernando Mayo-Merino, Leticia Olavarrieta, Luis A Aguirre, Ignacio del Castillo, Karen P Steel, Tamas Dalmay, Felipe Moreno, Miguel Angel Moreno-Pelayo

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Mutations in the seed region of human miR-96 are responsible for nonsyndromic progressive hearing loss

Angeles Mencía et al. Nat Genet. 2009 May.

Abstract

MicroRNAs (miRNAs) bind to complementary sites in their target mRNAs to mediate post-transcriptional repression, with the specificity of target recognition being crucially dependent on the miRNA seed region. Impaired miRNA target binding resulting from SNPs within mRNA target sites has been shown to lead to pathologies associated with dysregulated gene expression. However, no pathogenic mutations within the mature sequence of a miRNA have been reported so far. Here we show that point mutations in the seed region of miR-96, a miRNA expressed in hair cells of the inner ear, result in autosomal dominant, progressive hearing loss. This is the first study implicating a miRNA in a mendelian disorder. The identified mutations have a strong impact on miR-96 biogenesis and result in a significant reduction of mRNA targeting. We propose that these mutations alter the regulatory role of miR-96 in maintaining gene expression profiles in hair cells required for their normal function.

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