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Hearing loss

Gene: MIR96

Amber List (moderate evidence)

MIR96 (microRNA 96)
EnsemblGeneIds (GRCh38): ENSG00000199158
EnsemblGeneIds (GRCh37): ENSG00000199158
OMIM: 611606, Gene2Phenotype
MIR96 is in 1 panel

4 reviews

Eleanor Williams (Genomics England Curator)

Comment on list classification: After review with the NHS GMS hearing specialist group on 2019-02-13 it was decided to rate this gene as Amber. 2 cases reported by Mencia et al 2009 with variants likely to be pathogenic.
Created: 27 Feb 2019, 10:27 a.m.
Associated with Deafness, autosomal dominant 50 (613074) in OMIM.

PMID: 19363479 - Mencia et al 2009 - 2 unrelated families with autosomal dominant deafness. Both had variants in one allele of MIR96 -miR96(+13 G>A) and miR96(+14 C>A) affecting the conserved 7-nt seed region of the mature sequence. Both mutations segregated with hearing impairment in the family and was not detected in 462 unrelated normal-hearing Spanish controls.

PMID: 22038834 - Solda et al 2012 - identified one putative novel mutation within the miR-96 gene in an Italian family with autosomal dominant NSHL. Although located outside the mature miR-96 sequence, the detected variant replaces a highly conserved nucleotide within the companion miR-96*, and is predicted to reduce the stability of the pre-miRNA hairpin. The miR-96(+57T>C) mutation was found in the heterozygous state in a patient with a family history of autosomal dominant progressive NSHL and was absent in all 839 normal-hearing controls. The variant segregates with the phenotype within the family, being present in all affected individuals and absent in the normal hearing individuals III-4 and IV-4. However, the variation is also present in the three normal-hearing proband's children - this may be due either to the age-relatedness of hearing loss in the family (all non-penetrants are below the average age of onset of the disease among affected relatives) or to incomplete penetrance. Functional studies indicate that this mutation alters the correct maturation of the precursor miR-96, leading to a decrease in the level of both its mature forms. However, a direct role of miR-96* in NSHL pathogenesis has still to be proved.

PMID: 30245029 - Azaiez et al 2018 - publication about the Deafness Variation Database (DVD) which is a comprehensive database to inform variant classification for deafness. Provides a single classification for each variant based on collected evidence and is curated by experts in genetic hearing loss to provide a single-source guide to variant interpretation. They report that chr7:129414553:A>G in MIR96 is classified as Unknown significance in DVD but rated as pathogenic in HGMD. Looking in DVD - http://deafnessvariationdatabase.org/gene_page/MIR96 - there are only 2 variants reported as pathogenic. I think these are the two reported in Mencia et al 2009.
Created: 27 Feb 2019, 10:25 a.m.

Emma Ashton (Great Ormond Street Hospital)

I don't know

Mencia et al 2009 PMID 19363479 two different microRNA mutations (+13 and +14 relative to transcription initiation site) segregating in two large families. First study to implicate a miRNA in a Mendelian disorder. Two other subsequent reports of +57 as pathogenic Solda et al 2012 PMID 22038834 and Azaiez et al 2018 PMID 30245029
Created: 17 Feb 2019, 4:35 p.m.

Ellen McDonagh (Genomics England Curator)

Added tag to explain why there is no Ensembl gene ID for this entity.
Created: 6 Jan 2017, 3:56 p.m.

Jun Shen (Harvard Medical School)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
#613074:Deafness, autosomal dominant 50[Hearing loss, sensorineural, progressive (all frequencies)Tinnitus, bilateral (in some patients)]

Publications

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Amber
  • Expert
  • UKGTN
Phenotypes
  • Deafness, autosomal dominant 50 613074
Tags
locus-type-rna-micro
OMIM
611606
Clinvar variants
Variants in MIR96
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

27 Feb 2019, Gel status: 2

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: MIR96 were changed from to Deafness, autosomal dominant 50 613074

27 Feb 2019, Gel status: 2

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: MIR96 were set to

27 Feb 2019, Gel status: 2

Set mode of inheritance

Eleanor Williams (Genomics England Curator)

Mode of inheritance for gene: MIR96 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

27 Feb 2019, Gel status: 2

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: mir96 has been classified as Amber List (Moderate Evidence).

24 Jun 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

MIR96 was added to Congenital hearing impairment (Profound/Severe)panel. Sources: UKGTN,Expert

24 Jun 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

MIR96 was added to Congenital hearing impairment (Profound/Severe)panel. Sources: UKGTN,Expert