Disease relevance of COCH

• High prevalence of symptoms of Menière's disease in three families with a mutation in the COCH gene [1].
• In this study, using a Japanese population, we performed a COCH mutation analysis in 23 patients from independent families with autosomal dominant hearing impairment, four of whom reported vestibular symptoms, and also in 20 Meniere's patients [2].
• Prevalence of COCH mutations worldwide is unknown, as there is no systematic screening effort for late-onset hearing disorders; however, to date, COCH mutations have been found on four continents and the possibility of COCH playing an important role in presbycusis and disorders of imbalance has been considered [3].
• OBJECTIVE: To evaluate audiometric and vestibular signs and symptoms in a new DFNA9 family [4].
• Characteristic eosinophilic deposits in DFNA9 affected inner ear structures could be the result of aberrant folding, secretion, or solubility of mutated cochlins, as in certain other pathological states in which misfolded proteins accumulate and aggregate causing toxicity [5].

High impact information on COCH

• COCH message, found at high levels in human cochlear and vestibular organs, occurs in the chicken inner ear in the regions of the auditory and vestibular nerve fibres, the neural and abneural limbs adjacent to the cochlear sensory epithelium and the stroma of the crista ampullaris of the vestibular labyrinth [6].
• These areas correspond to human inner ear structures which show histopathological findings of acidophilic ground substance in DFNA9 patients [6].
• DFNA9 is an autosomal dominant, nonsyndromic, progressive sensorineural hearing loss with vestibular pathology [6].
• Here we report three missense mutations in human COCH (previously described as Coch5b2), a novel cochlear gene, in three unrelated kindreds with DFNA9 [6].
• All three residues mutated in DFNA9 are conserved in mouse and chicken Coch, and are found in a region containing four conserved cysteines with homology to a domain in factor C, a lipopolysaccharide-binding coagulation factor in Limulus polyphemus [6].

Chemical compound and disease context of COCH

• A novel DFNA9 mutation in the vWFA2 domain of COCH alters a conserved cysteine residue and intrachain disulfide bond formation resulting in progressive hearing loss and site-specific vestibular and central oculomotor dysfunction [7].

Biological context of COCH

• Missense mutations in the COCH gene, which is expressed preferentially at high levels in the inner ear, cause the autosomal dominant sensorineural deafness and vestibular disorder, DFNA9 (OMIM 601369) [8].
• A polyclonal antibody against the human COCH protein product, cochlin, was raised against the N-terminal 135 amino acid residues of cochlin, corresponding to the Limulus factor C-homology (cochFCH) domain; this domain harbors all five known point mutations in DFNA9 [8].
• The mutant serine at position 51 is situated between cysteines and possibly interferes with proper COCH protein folding or its interaction with extracellular matrix proteins [9].
• We have used the biological system of transient transfections of the entire protein coding region of COCH into several mammalian cell lines, to investigate various functional properties of cochlin [5].
• OBJECTIVE: To describe the decline of vestibulocochlear function in a man with vestibulocochlear dysfunction caused by a Pro51Ser mutation within the COCH gene on chromosome 14q12-13 (DFNA9) [10].

Anatomical context of COCH

• The fibrocytes expressing mRNA and protein products of COCH are the very cell types which are either absent or markedly reduced and replaced by eosinophilic acellular material in temporal bone sections of individuals affected with DFNA9 [8].
• By in situ hybridization of mouse and human inner ear sections, we find high-level expression of COCH mRNA in the fibrocytes of the spiral limbus and of the spiral ligament in the cochlea, and in the fibrocytes of the connective tissue stroma underlying the sensory epithelium of the crista ampullaris of the semicircular canals [8].
• METHODS: History, examination, and audiometric testing in the proband, brother, and son; quantitative rotational testing in the proband and son; histopathology of the cochlea and vestibular labyrinth in the proband; sequencing candidate genes COCH and MYO7A in the brother and son [11].
• In the vestibular system, a progressive horizontal canal hypofunction and a probable saccular otolith challenge were detected in family members with the c.1625G > T COCH alteration [7].
• Southern blot analysis of RT-PCR products detected a high level of COCH mRNA in the inner ear, lower level in spleen, and very low levels in the cerebrum, cerebellum/brain stem, eye, liver and kidney [12].

Associations of COCH with chemical compounds

• We identified a new point mutation, 253 T>A, in the coding region of the COCH gene, changing the isoleucine 109 to an asparagine (I109N) [13].

Other interactions of COCH

• A Pro51Ser mutation in the COCH gene is associated with late onset autosomal dominant progressive sensorineural hearing loss with vestibular defects [9].
• No mutations were found in the COCH or MYO7A genes [11].
• Speech recognition scores were compared with those of DFNA2, DFNA5, DFNA9, and presbyacusis subjects [14].
• Partial sequence analysis of Coch-5B2 reveals a von Willebrand factor type A-like domain in this cDNA [15].
• A few of the TZ-specific genes, including ASPA, FLJ10970 and COCH, were also stroma-specific [16].

Analytical, diagnostic and therapeutic context of COCH

• Sequence analysis revealed a 208C-->T mutation in the COCH gene, resulting in a Pro51Ser substitution in the predicted protein in all affected individuals of the family but not in unaffected family members and 200 control individuals [9].
• Exons 4 and 5 of the COCH gene were amplified by PCR reaction, using primer pairs flanking both exons [17].
• No differences were found in the nucleotide sequences of exons 4 and 5 in the COCH gene in patients with definite sporadic MD when they were compared with the control group [17].
• RESULTS: At the transcriptional level, COCH mRNA was detected only in the inner ear by RT-PCR [12].
• METHODS: COCH gene expression was studied by RT-PCR and Southern blot analysis [12].

References