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Hearing loss

Gene: COCH

Green List (high evidence)

COCH (cochlin)
EnsemblGeneIds (GRCh38): ENSG00000100473
EnsemblGeneIds (GRCh37): ENSG00000100473
OMIM: 603196, Gene2Phenotype
COCH is in 3 panels

7 reviews

Eleanor Williams (Genomics England Curator)

Green List (high evidence)

Comment on mode of inheritance: Leaving mode of inheritance as Monoallelic only for now, but with recommendation that it should be changed to BOTH monoallelic and biallelic, autosomal or pseudoautosomal at the next GMS review.
Created: 26 Nov 2020, 2:45 p.m. | Last Modified: 26 Nov 2020, 2:45 p.m.
Panel Version: 2.125
Reports of 7 families with homozygous or compound het variants in COCH. All appear to result in loss of function (the missense and inframe deletion variants affecting splicing) which is different to the GOF/dominant negative mechanism proposed for the monoallelic variants.

PMID: 29449721 - JanssensdeVarebeke et al 2018 - report 2 Belgian/Moroccan brothers with congenital prelingual deafness. They were found to have a homozygous nonsense variant in COCH c.292C>T(p.Arg98*). The heterozygous parents and sibling have normal hearing, apart from the mother. She presents with vestibular hyporeflexia and abnormal smooth pursuit tests. The patients reported here show an earlier onset of hearing impairment and vestibular dysfunction compared to individuals with dominant hearing loss causing COCH variants.

PMID: 31126177 - Mehregan et al 2019 - report an Iranian family with hereditary HL in which a homozygous variant (c.116T>A, p.L39X) in the COCH gene identified through WES.

PMID: 32562050 - Booth et al 2020 - report 4 families (1 Pakistani, 1 European, 1 Middle Eastern, 1 unknown ancestry) with ARSNHL. Four novel pathogenic variants (two nonsense variants, one missense, and one inframe deletion) were identified. Using minigene splicing assays they showed that both the missense and inframe deletion variants altered RNA splicing by creating an exon splicing silencer and abolishing an exon splicing enhancer, respectively. This would then create frameshifts and are predicted to result in a null allele.

PMID: 32939038 - Danial-Farran et al 2020 - report on 3 members of a Christian Arab family from northern Israel who are hearing imparied (high-tone hearing loss, ranging from mild-moderate in low frequencies to severe in high frequencies). All 3 members were diagnosed before the age of 2. A homozygous variant, c.984_985dup in COCH was identified by WES of the initial proband. Although transcripts with the variant were detected, only wild type protein was detected.
Created: 26 Nov 2020, 2:39 p.m. | Last Modified: 26 Nov 2020, 2:39 p.m.
Panel Version: 2.122

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Deafness, autosomal recessive 110 OMIM:618094; Deafness, autosomal dominant 9 OMIM:601369; deafness, autosomal recessive 110 MONDO:0054860; autosomal dominant nonsyndromic deafness 9 MONDO:0011058

Publications

Zornitza Stark (Australian Genomics)

Green List (high evidence)

Mono-allelic variants: Over 50 affected individuals from more than 10 families reported, mouse model. Dominant negative effect postulated.

Bi-allelic variants: three families reported with bi-allelic variants in this gene and deafness. All variants are LOF, some functional data. PMIDs 29449721, 32939038, 32562050.
Created: 5 Oct 2020, 9:07 a.m. | Last Modified: 5 Oct 2020, 9:07 a.m.
Panel Version: 2.94

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Deafness, autosomal dominant 9, MIM# 601369; Deafness, autosomal recessive 110, MIM# 618094

Publications

Lampros Mavrogiannis (Leeds Genetics Laboratory)

Green List (high evidence)

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

Maria Bitner-Glindzicz (UCL)

Green List (high evidence)

Ellen McDonagh (Genomics England Curator)

New review confirms gene status and mode of inheritance; no changes required.
Created: 11 Oct 2018, 1:42 p.m.
Comment on mode of inheritance: Not on the imprinted gene list.
Created: 17 Feb 2016, 12:48 p.m.

Jun Shen (Harvard Medical School)

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

Phenotypes
#601369:Deafness, autosomal dominant 9[Hearing loss, postlingualVestibular involvement (variable)VertigoTinnitusDownward sloping audiogramSuperior semicircular canal dehiscence (SCCD)Temporal bone shows deposition of cochlin-positive eosinophilic extracellular ground substance in the channels of the cochlear and vestibular nervesAtrophy of cochlear and vestibular fibrocytes]

Publications

Damian Smedley (Genomics England Curator)

Comment when marking as ready: Expert review and OMIM confirmed
Created: 29 Jan 2016, 3:06 p.m.

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Expert
  • Emory Genetics Laboratory
  • Radboud University Medical Center, Nijmegen
  • UKGTN
  • Illumina TruGenome Clinical Sequencing Services
Phenotypes
  • Deafness, autosomal recessive 110 OMIM:618094
  • Deafness, autosomal dominant 9 OMIM:601369
  • deafness, autosomal recessive 110 MONDO:0054860
  • autosomal dominant nonsyndromic deafness 9 MONDO:0011058
Tags
for-review
OMIM
603196
Clinvar variants
Variants in COCH
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

26 Nov 2020, Gel status: 3

Set mode of inheritance

Eleanor Williams (Genomics England Curator)

Mode of inheritance for gene: COCH was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

26 Nov 2020, Gel status: 3

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: COCH were set to PMID: 10400989; 11332404; 11709536; 12928864; 14512963; 16078052; 16261627; 16481359; 18312449; 19161137; 20097680; 22139968; 23684986; 7829101; 8817345; 9441737; 9806553; 9931344

26 Nov 2020, Gel status: 3

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: COCH were changed from hearing loss; #601369:Deafness, autosomal dominant 9; Nonsyndromic Hearing Loss, Dominant to Deafness, autosomal recessive 110 OMIM:618094; Deafness, autosomal dominant 9 OMIM:601369; deafness, autosomal recessive 110 MONDO:0054860; autosomal dominant nonsyndromic deafness 9 MONDO:0011058

26 Nov 2020, Gel status: 3

Added Tag

Eleanor Williams (Genomics England Curator)

Tag for-review tag was added to gene: COCH.

17 Feb 2016, Gel status: 4

Set Phenotypes

Ellen McDonagh (Genomics England Curator)

Phenotypes for COCH were set to hearing loss; #601369:Deafness, autosomal dominant 9; Nonsyndromic Hearing Loss, Dominant

17 Feb 2016, Gel status: 4

Set Phenotypes

Ellen McDonagh (Genomics England Curator)

Phenotypes for COCH were set to hearing loss; #601369:Deafness, autosomal dominant 9; Nonsyndromic Hearing Loss, Dominant; Nonsyndromic Hearing Loss, Dominant

17 Feb 2016, Gel status: 4

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for COCH were set to PMID: 10400989; 11332404; 11709536; 12928864; 14512963; 16078052; 16261627; 16481359; 18312449; 19161137; 20097680; 22139968; 23684986; 7829101; 8817345; 9441737; 9806553; 9931344

17 Feb 2016, Gel status: 4

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Mode of inheritance for COCH was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

29 Jan 2016, Gel status: 4

Gene classified by Genomics England curator

Damian Smedley (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

24 Jun 2015, Gel status: 4

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene COCH was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

24 Jun 2015, Gel status: 4

Added New Source

Ellen McDonagh (Genomics England Curator)

COCH was added to Congenital hearing impairment (Profound/Severe)panel. Sources: Illumina TruGenome Clinical Sequencing Services,UKGTN,Radboud University Medical Center, Nijmegen,Emory Genetics Laboratory,Expert

24 Jun 2015, Gel status: 4

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene COCH was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

24 Jun 2015, Gel status: 4

Added New Source

Ellen McDonagh (Genomics England Curator)

COCH was added to Congenital hearing impairment (Profound/Severe)panel. Sources: Illumina TruGenome Clinical Sequencing Services,UKGTN,Radboud University Medical Center, Nijmegen,Emory Genetics Laboratory,Expert

24 Jun 2015, Gel status: 3

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene COCH was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

24 Jun 2015, Gel status: 3

Added New Source

Ellen McDonagh (Genomics England Curator)

COCH was added to Congenital hearing impairment (Profound/Severe)panel. Sources: Illumina TruGenome Clinical Sequencing Services,UKGTN,Radboud University Medical Center, Nijmegen,Emory Genetics Laboratory,Expert

24 Jun 2015, Gel status: 2

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene COCH was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

24 Jun 2015, Gel status: 2

Added New Source

Ellen McDonagh (Genomics England Curator)

COCH was added to Congenital hearing impairment (Profound/Severe)panel. Sources: Illumina TruGenome Clinical Sequencing Services,UKGTN,Radboud University Medical Center, Nijmegen,Emory Genetics Laboratory,Expert

24 Jun 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

COCH was added to Congenital hearing impairment (Profound/Severe)panel. Sources: Illumina TruGenome Clinical Sequencing Services,UKGTN,Radboud University Medical Center, Nijmegen,Emory Genetics Laboratory,Expert