The Prevalence and Clinical Characteristics of MYO3A-Associated Hearing Loss in 15,684 Hearing Loss Patients
- Genes (Basel). 2025 Jan 16;16(1):92. doi: 10.3390/genes16010092.
- 1. Department of Hearing Implant Sciences, Shinshu University School of Medicine, Matsumoto 390-8621, Japan.
- 2. Department of Otolaryngology-Head and Neck Surgery, Tohoku University School of Medicine, Sendai 980-8575, Japan.
- 3. Department of Otorhinolaryngology-Head and Neck Surgery, Tokyo Medical University, Tokyo 160-0023, Japan.
- 4. Department of Otorhinolaryngology-Head and Neck Surgery, Keio University School of Medicine, Tokyo 160-8582, Japan.
- 5. Department of Otorhinolaryngology, Juntendo University, Tokyo 113-8421, Japan.
- 6. Department of Otorhinolaryngology, Tokai University School of Medicine, Isehara 259-1193, Japan.
- 7. Department of Ear Nose and Throat-Head and Neck Surgery, Wakayama Medical University, Wakayama 641-0012, Japan.
Background/Objectives:MYO3A 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 MYO3A have been reported to cause the deformation of hair cells into abnormally long stereocilia with an increase in spacing. MYO3A 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 MYO3A variations. Methods: 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 MYO3A variants. Results: We identified eight causative MYO3A variants by massively parallel DNA Sequencing, including six novel variants, and reported nine individuals possessing MYO3A gene variants, which is the largest group of non-related patients yet to be detected. Our findings confirmed that MYO3A variants cause progressive hearing loss, with its onset varying from birth to the second decade, eventually leading to severe-to-profound hearing loss. Conclusions: We clarified that patients with MYO3A 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 MYO3A gene variants and to provide intervention in a timely manner.