Clinical Details of Low-Frequency Hearing Loss Observed in Autosomal Dominant MYO7A-Associated Hearing Loss Patients

Background/Objectives: MYO7A is known to be the genetic cause of Usher syndrome type 1, as well as autosomal dominant and autosomal recessive non-syndromic hearing loss. In general, autosomal dominant MYO7A-associated hearing loss shows progressive high-frequency, sloping hearing loss. However, several variants are associated with low-frequency hearing loss. MYO7A-associated low-frequency hearing loss is relatively rare, and the clinical details remain unclear. Methods: A total of 18,475 Japanese patients with hearing loss were recruited. Targeted massively parallel sequencing of 158 deafness-related genes was performed, and individuals with variants related to MYO7A-associated low-frequency hearing loss were identified. Results: Among 18,475 hearing loss patients, we identified 60 patients from 44 unrelated families carrying five variants (p.[Asn140Lys; Glu1835Gln], p.Leu479Pro, p.Leu656Val, p.Gly660Arg, and p.Arg668His) for MYO7A-associated low-frequency hearing loss. Patients identified in this study initially showed postlingual-onset mild-to-moderate low-frequency hearing loss; however, high-frequency hearing also deteriorated after the fourth decade, eventually leading to moderate-to-severe flat-type hearing loss. In addition, we performed haplotype analysis for the recurrent variant c.1436T>C:p.Leu479Pro identified in this study and found that this variant is a founder mutation in the Japanese population. Conclusions: In this study, we were able to clarify the specific features of MYO7A-related low-frequency hearing loss in a significant number of patients. In particular, we clarified the details of hearing deterioration at each frequency. Our findings will be useful for providing more appropriate treatment and follow-up for MYO7A-associated low-frequency hearing loss.