Distribution of type IV collagen in the cochlea in Alport syndrome

Objective: To determine the distribution of alpha 1, alpha 3, and alpha 5 chains of type IV collagen in the cochlea in Alport syndrome. Design: Case-control study. Patients: Two patients with sensorineural hearing loss due to Alport syndrome. Both patients had known mutations in the COL4A5 gene. Main Outcome Measures: Immunostaining was used to study the distribution of type IV collagen (alpha 1, alpha 3, and alpha 5 chains) within the cochlea. Immunostaining was also performed in the cochlear tissues of an unaffected individual used as a control. Results: In the control ear, alpha 1 staining was observed in the basement membrane overlying the basilar membrane, in the basement membrane of cochlear blood vessels and Schwarm cells, and within the spiral limbus. In the control ear, we also observed strong staining for alpha 3 and alpha 5 chains in the basement membrane overlying the basilar membrane and within the spiral ligament. In both cases with Alport syndrome, no immunostaining was observed for alpha 3 or alpha 5 chains within the cochlea, whereas alpha 1 staining was present in locations similar to that seen in the control ear. Conclusions: The results indicate that isotype switching does not occur within the cochlea in Alport syndrome. The results are also consistent with the hypothesis that the sensorineural hearing loss in Alport syndrome may be due to alterations in cochlear micromechanics and/or dysfunction of the spiral ligament.