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

@article{Mencia2009MutationsIT,
  title={Mutations in the seed region of human miR-96 are responsible for nonsyndromic progressive hearing loss},
  author={Angeles Mencía and Silvia Modamio-H{\o}ybj{\o}r and Nick Redshaw and Mat{\'i}as Mor{\'i}n and Fernando Mayo-Merino and Leticia Olavarrieta and Luis A. Aguirre and Ignacio Del Castillo and Karen P. Steel and Tam{\'a}s Dalmay and Felipe Moreno and Miguel Angel Moreno-Pelayo},
  journal={Nature Genetics},
  year={2009},
  volume={41},
  pages={609-613}
}
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… 

A novel mutation within the MIR96 gene causes non-syndromic inherited hearing loss in an Italian family by altering pre-miRNA processing

Further evidence of the involvement of miR-96 mutations in human deafness is provided and it is demonstrated that a quantitative defect of this miRNA may contribute to NSHL.

miRNA mutations are not a common cause of deafness

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

Gain-of-function mutation of microRNA-140 in human skeletal dysplasia

The first case of a pathogenic gain-of-function miRNA mutation is presented and molecular insight into neomorphic actions of emerging and/or mutant miRNAs is provided, which may explain the potent target repression and robust in vivo effect by this mutant miRNA.

An ENU-induced mutation of miR-96 associated with progressive hearing loss in mice

This is the first microRNA found associated with deafness, and diminuendo represents a model for understanding and potentially moderating progressive hair cell degeneration in hearing loss more generally.

Independent Origin of c.57 C > T Mutation in MIR184 Associated with Inherited Corneal and Lens Abnormalities

It is hypothesized that genomic variants in the gene targets of MIR184 may act as nuclear modifier(s) leading to intra- and interfamily variability of age of onset and clinical symptoms, and to identify SNPs which could potentially modify phenotype severity in the members of the Galician family.

Germline deletion of the miR-17 ~ 92 cluster causes skeletal and growth defects in humans

These findings identify a regulatory function for miR7~92 in growth and skeletal development and represent the first example of an miRNA gene responsible for a syndromic developmental defect in humans.

Chromosome 1p21.3 microdeletions comprising DPYD and MIR137 are associated with intellectual disability

D dosage effects of MIR137 are associated with 1p21.3 microdeletions and may therefore contribute to the ID phenotype in patients with deletions harbouring this miRNA, and significant enrichment of miR-137 at the synapses of cortical and hippocampal neurons is demonstrated, suggesting a role of miRNAs in regulating local synaptic protein synthesis machinery.

Germline deletion of the miR-17-92 cluster causes growth and skeletal defects in humans

These findings identify a regulatory function for miR-17∼92 in growth and skeletal development and represent the first example of an miRNA gene responsible for a syndromic developmental defect in humans.

Hearing impairment due to Mir183/96/182 mutations suggests both loss and gain of function effects

A new bioinformatic tool for creating a causal network connecting transcriptional regulators to their misregulated genes using publicly available data (PoPCoRN) to aid analysis of RNAseq data from the two new mutants suggests the more severe phenotype of Mir96Dmdo mutants compared with Mir183/96 mutants is likely to be mediated by the gain of novel target genes in addition to the loss of its normal targets.
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