Temporal bone histopathology in connexin 26-related hearing loss

Objective: Mutations in GJB2, a gene that encodes a gap junction protein, C onnexin 26 (Cx26), are responsible for approximately one third of sporadic severe-to-profound or profound congenital deafness and half of severe-to-pr ofound or profound autosomal recessive nonsyndromic hearing loss (ARNSHL), Mouse mutants homozygous for knockouts of this gene are nonviable, precludi ng histopathologic studies of the associated inner ear pathology in this an imal model. Therefore, we studied archival temporal bone sections to identi fy temporal bone donors with Cx26-related deafness. Study Design: Temporal bone donors with a history of congenital severe-to-profound or profound dea fness were identified in the registry of the Temporal Bone Library at the U niversity of Iowa. Histological findings mere interpreted in a blinded fash ion. DNA extracted from two celloidin-embedded mid-modiolar sections from e ach temporal bone was screened for the 35delG Cx26 mutation. The entire cod ing region of Cx26 was screened for other deafness-causing mutations if the 35delG mutation was detected. Results: Of five temporal bone donors with c ongenital severe-to-profound deafness, one donor was found to have Cx26-rel ated deafness. This individual was a Cx26 compound heterozygote, carrying t he 35delG; mutation and a noncomplementary Cx26 missense mutation on the op posing allele, Microscopic evaluation of this temporal bone showed no neura l degeneration, a good population of spiral ganglion cells, near-total dege neration of hair cells in the organ of Corti, a detached and rolled-up tect orial membrane, agenesis of the stria vascularis, and a large cyst in the s cala media in the region of the stria vascularis, Conclusion: This study is the first to report the temporal bone histopathology associated with Cx26- related deafness. Preservation of neurons in the spiral ganglion suggests t hat long-term successful habilitation with cochlear implants may be possibl e in persons with severe-to-profound or profound Cx26-related deafness.