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Hearing loss

Gene: CLIC5

Amber List (moderate evidence)

CLIC5 (chloride intracellular channel 5)
EnsemblGeneIds (GRCh38): ENSG00000112782
EnsemblGeneIds (GRCh37): ENSG00000112782
OMIM: 607293, Gene2Phenotype
CLIC5 is in 1 panel

5 reviews

Eleanor Williams (Genomics England Curator)

Comment on list classification: Downgrading the rating from green to amber as upon review there was only 1 case, plus some functional data from mouse.
Created: 9 Jul 2019, 9:11 a.m. | Last Modified: 9 Jul 2019, 9:11 a.m.
Panel Version: 1.117
Checking with the Genomics England clinical team about the rating of this gene.
Created: 10 Apr 2019, 2:37 p.m.
This gene has a provisional association with ?Deafness, autosomal recessive 103 (616042) in OMIM.

PMID: 30575790 - Geng et al 2018 - Characterized a loss-of-function mutant mouse model (miR-183CGT/GT), in which the miR-183/96/182 cluster gene is inactivated by a gene-trap (GT) construct. The homozygous mutant mice show profound congenital hearing loss with severe defects in cochlear hair cell (HC) maturation, alignment, hair bundle formation and the checkboard-like pattern of the cochlear sensory epithelia. Several predicted target genes of the miR-183/96/182 cluster that are known to play important roles in HC development and function, including Clic5, Rdx, Ezr, Rac1, Myo1c, Pvrl3 and Sox2, are upregulated in the cochlea.

PMID: 24781754 - Seco et al 2015 - 2 sibs, born of consanguineous Turkish parents, with early-onset autosomal recessive deafness-103 with a homozygous truncating mutation in the CLIC5 gene. The mutation, which was found by homozygosity mapping and candidate gene sequencing, segregated with the disorder in the family. Screening for mutations in the CLIC5 gene in over 200 mostly Dutch or Spanish probands with hearing impairment did not identify any other mutations.

PMID: 24285636 Salles et al 2014 - Further work on the Jitterbug mouse model - Confocal and scanning electron microscopy of CLIC5-deficient jitterbug (jbg) mice revealed progressive fusion of stereocilia as early as postnatal day 10. Radixin (RDX), protein tyrosine phosphatase receptor Q (PTPRQ), and taperin (TPRN), deafness-associated proteins that also concentrate at the base of stereocilia, were mislocalized in fused stereocilia of jbg mice.

PMID: 17021174 - Gagnon et al 2006 - From OMIM: 'Jitterbug' (jbg/jbg) mutant mouse is an autosomal recessive phenotype characterized by overt head-bobbing and circling behavior with an inability to swim, indicating vestibular dysfunction. Mutant mice also show hearing loss that progresses to complete deafness. Linkage analysis and candidate gene analysis identified the cause of the phenotype as a homozygous intragenic deletion in the Clic5 gene that resulted in a truncated protein.

Only 1 family plus some functional data from mouse.
Created: 10 Apr 2019, 2:10 p.m.

Alistair Pagnamenta (University of Oxford)

I don't know

I don't think this association was replicated in humans yet and original family is small - the gene also only scores 7 on a recently published rating schema so only just makes it into "moderate" category - see https://search.clinicalgenome.org/kb/gene-validity/9545

So query whether evidence is sufficient for a green rating in PanelApp?
Created: 22 Mar 2019, 1:35 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Nonsyndromic sensorineural deafness

Publications

Jun Shen (Harvard Medical School)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
#616042:?Deafness, autosomal recessive 103[Hearing loss, sensorineuralDownsloping audiogramVestibular areflexiaVestibular dysfunction]

Publications

Damian Smedley (Genomics England Curator)

Comment on list classification: Good evidence from OMIM and expert
Created: 1 Feb 2016, 4:53 p.m.

Maria Bitner-Glindzicz (UCL)

Green List (high evidence)

Would want to report a Tier 1 variant
Created: 19 Oct 2015, 6:22 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • Expert
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • #616042:?Deafness, autosomal recessive 103
  • PMID: 24781754 (Nijjmegen group) progressive hearing impairment, vestibular and possibly mild renal dysfunction
OMIM
607293
Clinvar variants
Variants in CLIC5
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

9 Jul 2019, Gel status: 2

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: clic5 has been classified as Amber List (Moderate Evidence).

17 Feb 2016, Gel status: 4

Set Phenotypes

Ellen McDonagh (Genomics England Curator)

Phenotypes for CLIC5 were set to #616042:?Deafness, autosomal recessive 103; PMID: 24781754 (Nijjmegen group) progressive hearing impairment, vestibular and possibly mild renal dysfunction

17 Feb 2016, Gel status: 4

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for CLIC5 were set to PMID:10793131; 17021174; 18028448; 24781754

1 Feb 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).

1 Feb 2016, Gel status: 4

Set Mode of Inheritance

Damian Smedley (Genomics England Curator)

Mode of inheritance for CLIC5 was changed to BIALLELIC, autosomal or pseudoautosomal

1 Feb 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: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

CLIC5 was added to Congenital hearing impairment (Profound/Severe)panel. Sources: Radboud University Medical Center, Nijmegen,Expert

24 Jun 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

CLIC5 was added to Congenital hearing impairment (Profound/Severe)panel. Sources: Radboud University Medical Center, Nijmegen,Expert