title: Screening mutations of OTOF gene in Chinese patients with auditory neuropathy, including a familial case of temperature-sensitive auditory neuropathy.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Otolaryngology/Head and Neck Surgery, Institute of Otolaryngology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China.
authors.forename: Da-Yong
authors.initials: DY
authors.lastname: Wang
authors.forename: Yi-Chen
authors.initials: YC
authors.lastname: Wang
authors.forename: Dominique
authors.initials: D
authors.lastname: Weil
authors.forename: Ya-Li
authors.initials: YL
authors.lastname: Zhao
authors.forename: Shao-Qi
authors.initials: SQ
authors.lastname: Rao
authors.forename: Liang
authors.initials: L
authors.lastname: Zong
authors.forename: Yu-Bin
authors.initials: YB
authors.lastname: Ji
authors.forename: Qiong
authors.initials: Q
authors.lastname: Liu
authors.forename: Jian-Qiang
authors.initials: JQ
authors.lastname: Li
authors.forename: Huan-Ming
authors.initials: HM
authors.lastname: Yang
authors.forename: Yan
authors.initials: Y
authors.lastname: Shen
authors.forename: Cindy
authors.initials: C
authors.lastname: Benedict-Alderfer
authors.forename: Qing-Yin
authors.initials: QY
authors.lastname: Zheng
authors.forename: Christine
authors.initials: C
authors.lastname: Petit
authors.forename: Qiu-Ju
authors.initials: QJ
authors.lastname: Wang
mesh_terms: D000818:Animals; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D006224:Cricetinae; D003412:Cricetulus; D003638:Deafness / Q000235:genetics*; D005091:Exons; D005190:Family; D034381:Hearing Loss / Q000235:genetics*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D013696:Temperature
chemical_list: D008565:Membrane Proteins; C118457:OTOF protein, human