Connexion

GENATLAS PHENOTYPE

last update : 04-04-2023

Symbol	DFNA9
Location	14q12
HGNC id	2814
Name	neurosensory deafness 9
Corresponding gene	COCH
related resource	Genetics hearing impairment
Other symbol(s)	MENID1
Main clinical features	non syndromic, postlingual, progressive sensorineural hearing loss associated with vestibular dysfunction associated in some families with episodes of vertigo, tinnitus, aural fullness, and hearing loss, fulfilling the clinical criteria for Menière disease
Genetic determination	autosomal dominant
Related entries	including DFN31 and Menière disease (omim: 156000)
Function/system disorder	ear
Type	disease

Gene product

Name

cochlear cochlin (COCH), mutations mostly in the FCH (LCCL) domain

Mechanism(s)

Gene mutation	Chromosome rearrangement	Effect	Comments

missense		abnormal protein/gain of function	C542F substitution in exon 12, disrupting cysteine-mediated disulfide bond formation, associated with oculomotor and vestibular dysfunction (nystagmus)

Remark(s)

mutations in the COCH gene are responsible for a significant fraction of patients with autosomal dominant inherited hearing loss accompanied by vestibular symptoms, but not for dominant hearing loss without vestibular dysfunction or sporadic Meniere disease

mutant cochlins fail to integrate correctly into the extracellular matrix of the cochlear and vestibular systems, leading to structural changes that are likely to have pronounced effects on the sensory function (PMID: 19013156))

binding of cochlin to GAG was diminished by all of the point mutations found in DFNA9 patients (PMID: 35901072))

Genotype/Phenotype correlations

mutation associated with superior semicircular canal dehiscence in any cases (PMID: 19161137))