Monogenic hearing loss
Gene: CLDN9
The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.Created: 30 Jan 2023, 10:16 a.m. | Last Modified: 30 Jan 2023, 10:16 a.m.
Panel Version: 3.7
Comment on list classification: Promoting from red to amber but with a green rating recommendation following GMS review. 3 unrelated cases plus mouse model and some functional data.Created: 10 Oct 2021, 12:21 p.m. | Last Modified: 10 Oct 2021, 12:21 p.m.
Panel Version: 2.195
Provisionally associated with ?Deafness, autosomal recessive 116 #619093 in OMIM based on PMID:31175426.
PMID:31175426 - Sineni et al 2019 - report on 3 affected member of a consanguineous family from Turkey with autosomal recessive nonsyndromic hearing loss. Using WGS a 1bp deletion (c.86delT) in CLDN9 predicted to cause a frameshift and produce a truncated protein (p.Leu29ArgfsTer4) was identified, which co-segregates with SNHL in the family. In vitro studies showed a difference in protein localization between wildtype and mutant protein. Mice-lacking Cldn9 have been shown to develop SNHL (PMID: 19696885)
PMID:34265170 - Ramzen et al 2021 - report 2 families with recessively inherited deafness with childhood or adolescent onset. 2 homozygous variants in CLDN9 were identified, 1 missense (c.475G>A;p.(Glu159Lys)), and one an amino acid duplication (c.370_372dupATC;p.(Ile124dup)) which is predicted to locally misfold CLDN9. In both families the variants segregated with hearing loss in family members tested, with only affected individuals being homozygous. mCherry tagged p.(Ile124dup) CLDN9 is not targeted to the HeLa cell membrane. Mouse studies show that Cldn9 expression increases from embryonic to postnatal development and persists in adult inner ears.Created: 10 Oct 2021, 12:11 p.m. | Last Modified: 10 Oct 2021, 12:11 p.m.
Panel Version: 2.191
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Deafness, autosomal recessive 116, OMIM:619093
Publications
Three unrelated families and mouse model support disease association.Created: 9 Aug 2021, 10:54 a.m. | Last Modified: 9 Aug 2021, 10:54 a.m.
Panel Version: 2.179
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Deafness, autosomal recessive 116, MIM#619093
Publications
CLDN9 is not associated with a phenotype entry in OMIM.Created: 9 Feb 2016, 10:05 a.m.
CLDN9 is not associated with a phenotype entry in OMIM.Created: 7 Feb 2016, 3:40 p.m.
Tag Q4_21_rating was removed from gene: CLDN9.
Source NHS GMS was added to CLDN9. Source Expert Review Green was added to CLDN9. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Gene: cldn9 has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: CLDN9 were changed from to Deafness, autosomal recessive 116, OMIM:619093; deafness, autosomal recessive 116, MONDO:0033670
Publications for gene: CLDN9 were set to
Mode of inheritance for gene: CLDN9 was changed from to BIALLELIC, autosomal or pseudoautosomal
Tag Q4_21_rating tag was added to gene: CLDN9.
CLDN9 was added to Congenital hearing impairment (Profound/Severe)panel. Sources: Expert