DFNA9/&lt;i&gt;COCH&lt;/i&gt; and Its Phenotype

Kemperman, Martijn H; Bom, S. J. H.; Lemaire, F. X.; Verhagen, W. I. M.; Huygen, P.L.M.; Cremers, C.W.R.J.

doi:10.1159/000066806

Cited by 18 publications

(18 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The extent of formal vestibular and auditory testing conducted for DFNA9 pedigrees harboring mutations within the LCCL domain varies for each family. In general, hearing loss and vestibular hypofunction are noticed later in life for other DFNA9 pedigrees, in some cases not until the fourth or fifth decade [reviewed in Kemperman et al, 2002]. The DFNA9 pedigree carrying the p.V66G cochlin mutation is an exception with an audiogram verifying hearing loss in a 21 year old [Halpin et al, 1996] and caloric, rotary, and platform testing documenting vestibular hypofunction in 32, 37, and 38 year old family members [Khetarpal, 2000].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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

Street

Kallman

Robertson

et al. 2005

American J of Med Genetics Pt A

View full text Add to dashboard Cite

Mutations within the COCH gene (encoding the cochlin protein) lead to auditory and vestibular impairment in the DFNA9 disorder. In this study, we describe the genetic mapping of progressive autosomal dominant sensorineural hearing loss first affecting high-frequency auditory thresholds within a human pedigree to the long arm of chromosome 14 in band q12. A maximal pairwise LOD score of 7.08 was obtained with marker D14S1021. We identified a c.1625G > T mutation in exon 12 of COCH that co-segregates with auditory dysfunction in the pedigree. The mutation results in a predicted p.C542F substitution at an evolutionarily conserved cysteine residue in the C-terminus of cochlin. The c.1625G > T transversion in COCH exon 12 represents the first reported mutation outside of the LCCL domain which is encoded by exons 4 and 5. The 542F mutant cochlin is translated and secreted by transfected mammalian cells. Western blot analysis under non-reducing and reducing conditions suggests that the 542F mutation alters intramolecular cochlin disulfide bond formation. 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. Abnormal central oculomotor test results in family members with the c.1625G > T COCH alteration imply a possible central nervous system change not previously noted in DFNA9 pedigrees harboring mutations within the LCCL domain.

show abstract

Section: Discussionmentioning

confidence: 99%

“…COCH is expressed in the human auditory and vestibular systems [Robertson et al, 1997]. Pedigrees with COCH mutations are reported to have at least a portion of family members suffering from both cochlear and vestibular dysfunction [reviewed in Kemperman et al, 2002].…”

Section: Introductionmentioning

confidence: 99%

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

Street

Kallman

Robertson

et al. 2005

American J of Med Genetics Pt A

View full text Add to dashboard Cite

show abstract

“…In addition to the familial history, the audiogram is useful in the clinical setting. The hearing loss of DFNA9 usually starts in high frequencies as shown in the age-related typical audiogram [23] . The possibility of a COCH mutation should also be considered in sporadic Ménière's disease cases [10] .…”

Section: Discussionmentioning

confidence: 99%

Expression of Cochlin in the Vestibular Organ of Rats

Ikezono

Shindo²,

Ishizaki³

et al. 2005

ORL

View full text Add to dashboard Cite

The COCH gene mutated in autosomal dominant sensorineural deafness (DFNA9) encodes cochlin, a major constituent of the inner ear extracellular matrix. Cochlin constitutes 70% of the inner ear protein and cochlin isoforms can be classified into three subgroups, p63s, p44s and p40s. Symptoms of some DFNA9 patients are consistent with those of Ménière’s disease. Here, we report the expression of cochlin in the vestibular organ of rats using isoform-specific antibodies that recognize all three isoforms. Cochlin is highly expressed in the stromata of the maculae of otolithic organs and cristae of semicircular canals, and in the channels in the bony labyrinth that transmit the dendritic innervation to the cristae and maculae. Cochlin cannot be detected in the sensory cells, dark cells, nor in the acellular structures, otolithic membrane or in the cupula. These findings support the theory that deposition of acidophilic substance in the inner ear caused by mutation of cochlin can induce a secondary retrograde dendritic degeneration of the vestibular nerves.

show abstract

“…Neuroepithelial degenerations of the organ of Corti, crista and macula, and the dendrites and ganglia of the cochlear and vestibular nerves are also seen in some DFNA9 cases. 21,27 Moreover, endolymphatic hydrops is absent in most DNFA9 specimens.…”

Section: Discussionmentioning

confidence: 99%

“…6,21 The predominant clinical features in MD are episodes of vertigo lasting minutes to hours associated with ipsilateral aural fullness, tinnitus and sensorineural hearing loss, and the presence of total deafness is unusual, whereas in DFNA9 the vestibular symptoms are more variable and most individuals do not describe vertigo attacks. The sensorineural hearing loss starts at high frequencies, with onset in the second to fourth decades of life and it progresses to anacusis.…”

Section: Discussionmentioning

confidence: 99%

Absence of COCH mutations in patients with Meniere disease

et al. 2004

View full text Add to dashboard Cite

Missense mutations in the coagulation factor C homology (COCH) gene (14q12 -q13) cause the autosomal dominant sensorineural hearing loss and vestibular disorder DFNA9 (OMIM 603196), and a high prevalence of symptoms of Meniere disease (MD) has been described in families with a mutation in the COCH gene. In this study, we search for mutations in the COCH gene in peripheral blood from patients with definite MD. DNA was extracted from peripheral blood cells of 30 individuals with MD and 30 controls. Exons 4 and 5 of the COCH gene were amplified by PCR reaction, using primer pairs flanking both exons. Sequences were analysed by a DNA sequencing system and compared with the published COCH cDNA sequence. 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. Patients with definite MD have a low prevalence of mutations in exons 4 and 5 of the COCH gene.

show abstract

DFNA9/<i>COCH</i> and Its Phenotype

Cited by 18 publications

References 0 publications

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

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

Expression of Cochlin in the Vestibular Organ of Rats

Absence of COCH mutations in patients with Meniere disease

Contact Info

Product

Resources

About