The Clinical Details of MYH9-Related Disease and DFNA17 in a Large Japanese Hearing Loss Cohort

<b>Background/Objectives</b>: <i>MYH9</i> gene variants cause <i>MYH9</i>-related disease (<i>MYH9</i>-RD), which is also known as Epstein syndrome, Fechtner syndrome, May-Hegglin anomaly, and Sebastian syndrome. <i>MYH9</i>-RD is characterized by sensorineural hearing loss, macrothrombocytopenia, thrombocytopenia, hematuria/proteinuria, glomerulonephritis, cataracts purpura, and mucosal bleeding. In addition, the <i>MYH9</i> gene is also known to be causative of autosomal dominant non-syndromic hearing loss (DFNA17). <i>MYH9</i>-RD is a relatively rare disorder, and the detailed clinical features and mutational spectra remain unclear. <b>Methods</b>: In this study, we performed next-generation sequencing analysis for 15,684 hearing loss patients and identified <i>MYH9</i>-associated hearing loss patients. Detailed clinical information was collected for these patients and summarized. <b>Results</b>: In this study, we identified 24 patients from 18 families with <i>MYH9</i>-associated hearing loss. We clarified the details of hearing deterioration observed in patients based on collected serial audiogram data. Some cases showed rapid hearing deterioration that worsened by about 50 dB within 5 years. Hearing loss is more likely to progress in patients with myosin head domain variants than in patients with myosin tail domain variants, but hearing loss in each set of patients finally deteriorates to bilateral profound hearing loss. <b>Conclusions</b>: In this study, we were able to clarify the detailed characteristics of <i>MYH9</i>-RD- and DFNA17-related hearing loss in a relatively large number of patients, particularly in some cases that showed rapid and asymmetrical hearing deterioration progressing to bilateral profound hearing loss. Our data will be useful for providing more appropriate treatment and follow-up for <i>MYH9</i>-associated hearing loss.