Histopathology of the Human Inner Ear in a Patient With Sensorineural Hearing Loss Caused by a Variant in DFNA5.
OBJECTIVE
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.
*Department of Otolaryngology, Massachusetts Eye and Ear Infirmary/Harvard Medical School, Boston, Massachusetts †Department of Otolaryngology/Head and Neck and Maxillofacial Surgery, Tel Aviv Sourasky Medical Center, Tel Aviv University, Tel Aviv, Israel ‡Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine, Cambridge §Department of Pathology, Brigham and Women's Hospital/Massachusetts General Hospital, Boston, Massachusetts, U.S.A.
Joseph B
JB
Nadol
Ophir
O
Handzel
Sami
S
Amr
D019929:Cochlear Implantation; D003054:Cochlear Implants; D007758:Ear, Inner / Q000473:pathology*; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000235:genetics / Q000473:pathology*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D011960:Receptors, Estrogen / Q000235:genetics*; D013701:Temporal Bone / Q000473:pathology; D000094524:Gasdermins
D011960:Receptors, Estrogen; C111432:GSDME protein, human; D000094524:Gasdermins