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A Dominant Mutation in the Stereocilia-Expressing Gene TBC1D24 is a Probable Cause for Nonsyndromic Hearing Impairment

Authors

  • Luping Zhang,

    1. Department of Otolaryngology—Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
    2. Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China
    3. Department of Otolaryngology—Head and Neck Surgery, Affiliated Hospital of Nantong University, Jiangsu, China
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    • These authors contributed equally to this work.

  • Lingxiang Hu,

    1. Department of Otolaryngology—Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
    2. Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China
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    • These authors contributed equally to this work.

  • Yongchuan Chai,

    1. Department of Otolaryngology—Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
    2. Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China
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  • Xiuhong Pang,

    1. Department of Otolaryngology—Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
    2. Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China
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  • Tao Yang,

    Corresponding author
    1. Department of Otolaryngology—Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
    2. Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China
    • Correspondence to: Hao Wu, Department of Otolaryngology—Head and Neck Surgery, Xinhua Hospital, 1665 Kongjiang Road, Shanghai 200092, China. E-mail: wuhao622@sina.cn; Tao Yang, 917 Science and Education Building, Xinhua Hospital, 1665 Kongjiang Road, Shanghai 200092, China. E-mail: yangtfxl@sina.com

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  • Hao Wu

    Corresponding author
    1. Department of Otolaryngology—Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
    2. Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China
    • Correspondence to: Hao Wu, Department of Otolaryngology—Head and Neck Surgery, Xinhua Hospital, 1665 Kongjiang Road, Shanghai 200092, China. E-mail: wuhao622@sina.cn; Tao Yang, 917 Science and Education Building, Xinhua Hospital, 1665 Kongjiang Road, Shanghai 200092, China. E-mail: yangtfxl@sina.com

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  • Communicated by Mark H. Paalman

  • Contract grant sponsor: National Basic Research Program of China (2011CB504501); National Science Foundation of China (81222010, 81371101, 81330023, 81170924, 81300821; China Postdoctoral Science Foundation (2013M5415127; The Six Major Human Resources Project of Jiangsu Province (2013-WSN-075); The Oriental Scholar project from Shanghai Municipal Education Commission.

ABSTRACT

Mutations in TBC1D24 have been linked to a variety of epileptic syndromes and recently to syndromic hearing impairment DOORS syndrome and nonsyndromic hearing impairment DFNB86. All TBC1D24 mutations reported so far were inherited in the recessive mode. In a dominant family segregated with late-onset, progressive, nonsyndromic hearing impairment, linkage analysis revealed a 2.07 Mb candidate region on chromosome 16p13.3 that contains TBC1D24. Whole-exome sequencing identified a heterozygous p.Ser178Leu variant of TBC1D24 as the only candidate mutation segregating with the hearing loss within the family. In perinatal mouse cochlea, we detected a restricted expression of Tbc1d24 in the stereocilia of the hair cells as well as in the spiral ganglion neurons. Our study suggested that the p.Ser178Leu mutation of TBC1D24 is a probable cause for dominant, nonsyndromic hearing impairment. Identification of TBC1D24 as the stereocilia-expressing gene may shed new light on its specific function in the inner ear.

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