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OTOF mutation screening in Japanese severe to profound recessive hearing loss patients

Yoh-ichiro Iwasa1, Shin-ya Nishio1, Hidekane Yoshimura1, Yukihiko Kanda2, Kozo Kumakawa3, Satoko Abe3, Yasushi Naito4, Kyoko Nagai5 and Shin-ichi Usami1*

Author Affiliations

1 Department of Otorhinolaryngology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan

2 Kanda ENT Clinic, 4-25 Wakakusa-cho, Nagasaki 852-8023, Japan

3 Department of Otorhinolaryngology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo 105-8470, Japan

4 Department of Otolaryngology, Kobe City Medical Center General Hospital, 2-1-1 Minatojima Minamimachi, Chuou-ku, Kobe City 650-0047, Japan

5 Department of Otorhinolaryngology, Gunma University School of Medicine, 3-39-15 Shouwa-machi, Maebashi, Gunma 371-8511, Japan

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BMC Medical Genetics 2013, 14:95  doi:10.1186/1471-2350-14-95

Published: 22 September 2013



Auditory neuropathy spectrum disorder (ANSD) is a unique form of hearing loss that involves absence or severe abnormality of auditory brainstem response (ABR), but also the presence of otoacoustic emissions (OAEs). However, with age, the OAEs disappear, making it difficult to distinguish this condition from other nonsyndromic hearing loss. Therefore, the frequency of ANSD may be underestimated. The aim of this study was to determine what portion of nonsyndromic hearing loss is caused by mutations of OTOF, the major responsible gene for nonsyndromic ANSD.


We screened 160 unrelated Japanese with severe to profound recessive nonsyndromic hearing loss (ARNSHL) without GJB2 or SLC26A4 mutations, and 192 controls with normal hearing.


We identified five pathogenic OTOF mutations (p.D398E, p.Y474X, p.N727S, p.R1856Q and p.R1939Q) and six novel, possibly pathogenic variants (p.D450E, p.W717X, p.S1368X, p.R1583H, p.V1778I, and p.E1803A).


The present study showed that OTOF mutations accounted for 3.2–7.3% of severe to profound ARNSHL patients in Japan. OTOF mutations are thus a frequent cause in the Japanese deafness population and mutation screening should be considered regardless of the presence/absence of OAEs.

Auditory neuropathy spectrum disorder; DFNB9; Nonsyndromic hearing loss