Histopathology of the Human Inner Ear in the p.L114P <b><i>COCH</i></b> Mutation (DFNA9)

Abstract

The histopathology of the inner ear in a patient with hearing loss caused by the p.L114P COCH mutation and its correlation with the clinical phenotype are presented. To date, 23 COCH mutations causative of DFNA9 autosomal dominant sensorineural hearing loss and vestibular disorder have been reported, and the histopathology of the human inner ear has been described in 4 of these. The p.L114P COCH mutation was first described in a Korean family. We have identified the same mutation in a family of non-Asian ancestry in the USA, and the temporal bone histopathology and clinical findings are presented herein. The histopathology found in the inner ear was similar to that shown in the 4 other COCH mutations and included degeneration of the spiral ligament with deposition of an eosinophilic acellular material, which was also found in the distal osseous spiral lamina, at the base of the spiral limbus, and in mesenchymal tissue at the base of the vestibular neuroepithelium. This is the first description of human otopathology of the COCH p.L114P mutation. In addition, it is the only case with otopathology characterization in an individual with any COCH mutation and residual hearing, thus allowing assessment of primary histopathological events in DFNA9, before progression to more profound hearing loss. A quantitative cytologic analysis of atrophy in this specimen and immunostaining using anti-neurofilament and anti-myelin protein zero antibodies confirmed that the principal histopathologic correlate of hearing loss was degeneration of the dendritic fibers of spiral ganglion cells in the osseous spiral lamina. The implications for cochlear implantation in this disorder are discussed.

Immunohistochemical techniques for the human inner ear

“…Aggrecan (extracellular component of cartilage), S100 and connective tissue growth factor were detected in the human temporal bones from individuals diagnosed with DFNA9 (McCall et al 2011). Changes in neurofilaments and myelin protein zero antibodies were detected in the cochlea of a patient with hearing loss caused by the p.L114P COCH mutation (Burgess et al 2016). Recent studies that apply IHC in human inner ear celloidin-embedded sections have shown the presence of specific markers for macrophages/microglia: CD163 + , Iba1 + and CD68 + (O’Malley et al 2015).…”

Evidence of Osteoclastic Activity in the Human Temporal Bone

“…All patients were selected from cases without other bone disease such as osteoporosis or Paget's disease and without inflammatory disease such as otitis media and labyrinthitis and they classified into 4 groups: histologically proven SSCD (n = 3, group 1), age 20 years or younger (n = 10, group 2), age 90 years or older with otosclerosis (n = 10, group 3), and age 90 years or older without otosclerosis (n = 10, group 4). The clinical histories of cases 1 and 2 with SSCD (group 1) have already been reported [Teixido et al, 2012;Burgess et al, 2016]. The clinical history and histologic findings of case 3 (group 1) are presented herein.…”

Contemporary techniques in human otopathology and promise for the future

“…The organ of Corti (OC) was seen. Source: Previously published 33 and reprinted with permission of Karger Publishers F I G U R E 7 Immunostaining following celloidin removal with methanol, saturated with sodium hydroxide. Immunostaining for six antibodies was accomplished.…”

“…Sanger sequencing of DNA can also be accomplished using frozen muscle obtained at autopsy of a temporal bone donor. Using this technique, the histopathology of the human inner ear caused by the p.L11p Coch mutation (DFNA9) was demonstrated (Figure ).…”

“…The organ of Corti (OC) was seen. Source : Previously published and reprinted with permission of Karger Publishers…”