Affordable Access

Publisher Website

Clinical Characteristics and In Vitro Analysis of MYO6 Variants Causing Late-Onset Progressive Hearing Loss.

  • Oka, Shin-Ichiro1
  • Day, Timothy F1
  • Nishio, Shin-Ya1, 2
  • Moteki, Hideaki1, 2
  • Miyagawa, Maiko1, 2
  • Morita, Shinya3
  • Izumi, Shuji4
  • Ikezono, Tetsuo5
  • Abe, Satoko6
  • Nakayama, Jun7
  • Hyogo, Misako8
  • Okamoto, Nobuhiko9
  • Uehara, Natsumi10
  • Oshikawa, Chie11
  • Kitajiri, Shin-Ichiro1, 2
  • Usami, Shin-Ichi1, 2
  • 1 Department of Otorhinolaryngology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan. , (Japan)
  • 2 Department of Hearing Implant Sciences, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan. , (Japan)
  • 3 Department of Otolaryngology-Head and Neck Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, North-15, West-7, Sapporo 060-8638, Japan. , (Japan)
  • 4 Department of Otolaryngology, Head and Neck Surgery, Niigata University Graduate School of Medical and Dental Sciences, Asahimachi 1, Niigata city, Niigata 951-8510, Japan. , (Japan)
  • 5 Faculty of Medicine, Otorhinolaryngology, Saitama Medical University, Morohongo 38, Moroyamamachi, Irumagun, Saitama-ken 350-0495, Japan. , (Japan)
  • 6 Department of Otorhinolaryngology, Toranomon Hosipital, 2-2-2 Toranomon, Minato-ku, Tokyo 105-8470, Japan. , (Japan)
  • 7 Department of Otorhinolaryngology, Shiga University School of Medical Science, Seta Tsukinowacho, Otsu 520-2192, Japan. , (Japan)
  • 8 Department of Otolaryngology-Head and Neck Surgery, Kyoto Prefectural University of Medicine, 465 Kagii-cho, Kyoto 602-8566, Japan. , (Japan)
  • 9 Department of Medical Genetics, Osaka Women's and Children's Hospital, 840 Murodo-cho, Izumi, Osaka 594-1101, Japan. , (Japan)
  • 10 Department of Otolaryngology-Head and Neck Surgery, Kobe University School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan. , (Japan)
  • 11 Department of Otorhinolaryngology-Head and Neck Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. , (Japan)
Published Article
Publication Date
Mar 04, 2020
DOI: 10.3390/genes11030273
PMID: 32143290


MYO6 is known as a genetic cause of autosomal dominant and autosomal recessive inherited hearing loss. In this study, to clarify the frequency and clinical characteristics of hearing loss caused by MYO6 gene mutations, a large-scale genetic analysis of Japanese patients with hearing loss was performed. By means of massively parallel DNA sequencing (MPS) using next-generation sequencing for 8074 Japanese families, we found 27 MYO6 variants in 33 families, 22 of which are novel. In total, 2.40% of autosomal dominant sensorineural hearing loss (ADSNHL) in families in this study (32 out of 1336) was found to be caused by MYO6 mutations. The present study clarified that most cases showed juvenile-onset progressive hearing loss and their hearing deteriorated markedly after 40 years of age. The estimated hearing deterioration was found to be 0.57 dB per year; when restricted to change after 40 years of age, the deterioration speed was accelerated to 1.07 dB per year. To obtain supportive evidence for pathogenicity, variants identified in the patients were introduced to MYO6 cDNA by site-directed mutagenesis and overexpressed in epithelial cells. They were then assessed for their effects on espin1-induced microvilli formation. Cells with wildtype myosin 6 and espin1 co-expressed created long microvilli, while co-expression with mutant constructs resulted in severely shortened microvilli. In conclusion, the present data clearly showed that MYO6 is one of the genes to keep in mind with regard to ADSNHL, and the molecular characteristics of the identified gene variants suggest that a possible pathology seems to result from malformed stereocilia of the cochlear hair cells.

Report this publication


Seen <100 times