Histopathology of the Human Inner Ear in a Patient With Sensorineural Hearing Loss Caused by a Variant in DFNA5

Abstract

Hypothesis: 

Describe the histopathology of the inner ear in a patient with hearing loss caused by a pathogenic variant of the DFNA5 gene.

Background: 

Variants in DFNA5 have been described as causing an autosomal dominant nonsyndromic sensorineural hearing loss. To date, there has been no description of the histopathology of the inner ear in humans with hearing loss because of pathogenic variants in DFNA5.

Methods: 

Temporal bone histopathology by light microscopy, next-generation sequencing (NGS) of DNA obtained from blood, and Sanger sequencing of DNA obtained from formalin fixed temporal bone sections.

Results: 

Both the temporal bone donor and her daughter were shown to have the same pathogenic variant in the DFNA5 gene. The principal histopathologic correlates of the hearing loss were loss of the inner and outer hair cells and severe degeneration of the stria vascularis and spiral ligament throughout the cochlea. In addition, there was severe degeneration of spiral ganglion cells, particularly in the basal turn, and degeneration of vestibular neuroepithelium and neurons. The donor had undergone unilateral cochlear implantation during life. Histopathology demonstrated that the cochlear implant was inserted into the scala vestibuli with considerable new bone formation around the track of the implanted electrode.

Conclusions: 

This is the first report of the histopathology of the inner ear in a patient with hearing loss caused by a pathogenic variant in the DFNA5 gene.