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

作者：Zhang, Luping; Hu, Lingxiang; Chai, Yongchuan; Pang, Xiuhong; Yang, Tao; Wu, Hao^*

来源：Human Mutation, 2014, 35(7): 814-818.

DOI：10.1002/humu.22558

• TBC1D24
• autosomal dominant
• nonsyndromic
• hearing impairment
• hearing loss
• stereocilia

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 2.07Mb 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.

• 出版日期2014-7
• 单位南通大学; 上海交通大学