Open Access Research article

Screening mutations of OTOF gene in Chinese patients with auditory neuropathy, including a familial case of temperature-sensitive auditory neuropathy

Da-Yong Wang1, Yi-Chen Wang2, Dominique Weil3, Ya-Li Zhao4, Shao-Qi Rao5, Liang Zong1, Yu-Bin Ji1, Qiong Liu1, Jian-Qiang Li1, Huan-Ming Yang2, Yan Shen47, Cindy Benedict-Alderfer6, Qing-Yin Zheng6, Christine Petit3 and Qiu-Ju Wang17*

  • * Corresponding author: Qiu-Ju Wang

  • † Equal contributors

Author Affiliations

1 Department of Otolaryngology/Head and Neck Surgery, Institute of Otolaryngology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China

2 Beijing Institute of Genomics, Chinese Academy of Sciences, No.7 Beitucheng West Road, Chaoyang District, Beijing 100029, China Graduate University of the Chinese Academy of Sciences, 19A Yu Quan Rd, Beijing 100049, China

3 Institut Pasteur, Inserm U587, Unité de Génétique et Physiologie de l'Audition, 25 rue du Docteur Roux, 75724 Paris Cedex 15, France

4 Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

5 Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China

6 Department of Otolaryngology-HNS, Case Western Reserve University, Cleveland, Ohio 44106, USA

7 Chinese National Human Genome Centre, Beijing 100176, China

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BMC Medical Genetics 2010, 11:79  doi:10.1186/1471-2350-11-79

Published: 26 May 2010



Mutations in OTOF gene, encoding otoferlin, cause DFNB9 deafness and non-syndromic auditory neuropathy (AN). The aim of this study is to identify OTOF mutations in Chinese patients with non-syndromic auditory neuropathy.


73 unrelated Chinese Han patients with AN, including one case of temperature sensitive non-syndromic auditory neuropathy (TS-NSRAN) and 92 ethnicity-matched controls with normal hearing were screened. Forty-five pairs of PCR primers were designed to amplify all of the exons and their flanking regions of the OTOF gene. The PCR products were sequenced and analyzed for mutation identification.


Five novel possibly pathogenic variants (c.1740delC, c.2975_2978delAG, c.1194T>A, c.1780G>A, c.4819C > T) were identified in the group of 73 AN patients, in which two novel mutant alleles (c.2975_2978delAG + c.4819C > T) were identified in one Chinese TS-NSRAN case. Besides, 10 non-pathogenic variants of the OTOF gene were found in AN patients and controls.


Screening revealed that mutations in the OTOF gene account for AN in 4 of 73(5.5%) sporadic AN patients, which shows a lower genetic load of that gene in contrast to the previous studies based on other populations. Notably, we found two novel mutant alleles related to temperature sensitive non-syndromic auditory neuropathy. This mutation screening study further confirms that the OTOF gene contributes to ANs and to TS-NSRAN.