The Prevalence and Clinical Characteristics of MYO3A-Associated Hearing Loss in 15,684 Hearing Loss Patients

<b>Background/Objectives:</b><i>MYO3A</i> belongs to the unconventional myosin superfamily, and the myosin IIIa protein localizes on the tip of the stereocilia of vestibular and cochlear hair cells. Deficiencies in <i>MYO3A</i> have been reported to cause the deformation of hair cells into abnormally long stereocilia with an increase in spacing. <i>MYO3A</i> is a rare causative gene of autosomal recessive sensorineural hearing loss (DFNB30), with only 13 cases reported to date. In this study, we aimed to elucidate the phenotypes caused by <i>MYO3A</i> variations. <b>Methods:</b> Massively parallel DNA sequencing was performed on 15,684 Japanese hearing loss patients (mean age 27.5 ± 23.1 years old, 6574 male, 8612 female and 498 patients for whom information was unavailable), identifying nine candidate patients with <i>MYO3A</i> variants. <b>Results:</b> We identified eight causative <i>MYO3A</i> variants by massively parallel DNA sequencing, including six novel variants, and reported nine individuals possessing <i>MYO3A</i> gene variants, which is the largest group of non-related patients yet to be detected. Our findings confirmed that <i>MYO3A</i> variants cause progressive hearing loss, with its onset varying from birth to the second decade, eventually leading to severe-to-profound hearing loss. <b>Conclusions:</b> We clarified that patients with <i>MYO3A</i> gene variants present with late-onset, progressive hearing loss. Our findings have enabled us to predict the outcomes of hearing loss in patients with candidate <i>MYO3A</i> gene variants and to provide intervention in a timely manner.