Abstract
OBJECTIVE: To characterize the audiometric phenotype of autosomal-dominant DFNA34 hearing loss (HL) caused by a missense substitution in the NLRP3 gene. NLRP3 encodes a critical component of the NLRP3 inflammasome that is activated in innate immune responses. STUDY DESIGN: This study was conducted under protocol 01-DC-0229 approved by the NIH Combined Neurosciences IRB. We performed medical and developmental history interviews and physical and audiological examinations of affected individuals with DFNA34 HL caused by the p.Arg918Gln mutation of NLRP3. We retrospectively reviewed audiological reports, when available, from other health care centers. SETTING: Federal biomedical research facility. SUBJECTS: Eleven members of a North American family segregating p.Arg918Gln. MAIN OUTCOME MEASURES: Pure-tone thresholds, rates of pure-tone threshold progression, and speech discrimination scores. RESULTS: Eight subjects had bilateral sensorineural HL with an onset in the late 2nd to 4th decade of life. Slowly progressive HL initially primarily affected high frequencies. Low and middle frequencies were affected with advancing age, resulting in moderate HL with a downsloping audiometric configuration. The average annual threshold deterioration was 0.9 to 1.5 dB/yr. Speech recognition scores ranging from 60 to 100% were consistent with cochlear, but not retrocochlear, etiology. Three subjects (16, 22, and 32 yr old) had normal hearing thresholds. CONCLUSION: DFNA34 HL has an onset during early adulthood and progresses approximately 1.2 dB/yr.