Family #32 was identified as having early-onset, progressive sensorineural hearing loss, similar to the symptoms in DFNA9 patients with cochlin mutations in the vWFA domain.
It is the first reported autosomal dominant nonsyndromic sensorineural deafness 9 (DFNA9) mutation outside the limulus factor C, cochlin and late gestation lung protein and von Willebrand factor 2 domain, i.e. the first reported DFNA9 mutation in the intervening domain of cochlin, encoded by the COCH gene.
We suggest that the instability of mutant cochlin is the major driving force for cochlin aggregation in the inner ear in DFNA9 patients carrying the COCH p.F527C mutation.
We suggest that the instability of mutant cochlin is the major driving force for cochlin aggregation in the inner ear in DFNA9 patients carrying the COCH p.F527C mutation.
Mutations in the COCH (coagulation factor C homology) gene have been attributed to DFNA9 (deafness, autosomal-dominant 9), an autosomal-dominant non-syndromic hearing loss disorder.
The study of clinical features of a DFNA9 family carrying a G88ECOCH mutation and to compare this to the symptoms of those carrying a P51S/COCH mutation.
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.
Our findings suggest that COCH mutations are unlikely to cause abnormalities in secretion and suggest that extracellular events might cause DFNA9 pathology.
Our findings suggest that COCH mutations are unlikely to cause abnormalities in secretion and suggest that extracellular events might cause DFNA9 pathology.
Unusual phenotypes in autosomal dominant forms of deafness, include low frequency hearing loss in DFNA1 (HDIA1) and DFNA6/14/38 (WFS1), mid-frequency hearing loss in DFNA8/12 (TECTA), DFNA13 (COL11A2) and vestibular symptoms and signs in DFNA9 (COCH) and sometimes in DFNA11 (MYO7A).