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Int J Clin Exp Pathol 2012;5(1):23-28

Review Article
c-Ret-mediated hearing losses

Nobutaka Ohgami, Haruka Tamura, Kyoko Ohgami, Machiko Iida, Ichiro Yajima, Mayuko Y. Kumasaka, Yuji Goto, Michihiko Sone, Tsutomu
Nakashima, Masashi Kato

Units of Environmental Health Sciences, Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, Kasugai,
Aichi, Japan; Department of Otorhinolaryngology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.

Received November 16, 2011; accepted December 13, 2011; Epub December 15, 2011; published January 15, 2012

Abstract: About 120 million people worldwide suffer from congenital (early-onset) hearing loss. Thirty percent of them have syndromic hearing
loss and the remaining 70% have non-syndromic hearing loss. In addition, a large number of elderly people worldwide suffer from age-related
(late-onset) hearing loss. c-Ret and c-RET have been shown to be essential for the development and maintenance of neurons including the
enteric nervous system (ENS) in mice and humans. Impairments of endothelin receptor B (EDNRB) and SOX10 have been shown to cause a
significantly increased risk of dominant sensorineural deafness in Hirschsprung disease (HSCR) patients. We have recently shown that
impairments of tyrosine 1062 (Y1062) phosphorylation in c-Ret causes syndromic congenital deafness in mice and humans and
non-syndromic age-related hearing loss with neurodegeneration of spiral ganglion neurons (SGNs) in mice. This review focuses on the
pathogenesis of hearing loss caused by impairments of c-Ret. (IJCEP1111009).

Keywords: c-Ret, congenital deafness, age-related deafness, tyrosine kinase, spiral ganglion neuron, neurodegeneration

Address all correspondence to:
Masashi Kato MD, PhD
Unit of Environmental Health Sciences
Department of Biomedical Sciences
College of Life and Health Sciences, Chubu University
No.50 building, 1200 Matsumoto, Kasugai, Aichi 487-8501, Japan.
Tel: +81-568-51-7364. Fax: +81-568-51-9635.
E-mail: katomasa@isc.chubu.ac.jp