Monogenic hearing loss

Gene: CLDN9

Green List (high evidence)

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

Green List (high evidence)

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

• 31175426
• 34265170

Green List (high evidence)

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

• 31175426
• 19696885
• 34265170

Red List (low evidence)

Red List (low evidence)

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.