Genetic predisposition of adult-onset and down-sloping sensorineural hearing loss.

Objective: Hereditary hearing loss is genetically very heterogeneous. Although congenital hearing loss is likely to be caused by genetic disposing factors, it is hard to distinguish inherited cases from non-inherited cases in sporadic hearing loss. Herein, we delineated the genetic inheritance in the cases of late-onset and down-sloping sensorineural hearing loss. Subjects and methods: Among the Korean adults (ranging from 20 to 60 years-old) with bilateral down-sloping non-syndromic sensorineural hearing loss (defined as patients with auditory thresholds at 1, 2, and 4 kHz more than 60dB HL and thresholds at 250 and 500 Hz less than 40 dB HL), subjects were enrolled if the onset of hearing loss was from 20 to 50 years-old-age. In temporal bone CT scan and MRI, there was no inner ear anomaly. Whole exome sequencing (WES) was performed to reveal the genetic variations associated with late-onset and down-sloping hearing loss. Results: Of the 18 unrelated families included in this study, genetic variations were identified in 5 probands. All subjects were negative of mutations in SLC26A4 and GJB2. According to the variation calling pipeline, we screened 182 known genes causing inherited hearing loss including syndromic and/ or non-syndromic patterns. As a result, missense mutations were identified in several candidate genes including MYH9, MYH14, and COL11A2. Conclusion: Genetic causes were identified in a relatively high proportion of patients showing adult-onset and progressive hearing loss with a down-sloping pattern which may be commonly ascribed to age-related or noise-induced hearing loss. Identification of the genetic cause of hearing loss in these patients may be used in counseling about the prognosis of cochlear implantation in those who progress to severe to profound hearing loss. [ABSTRACT FROM AUTHOR]