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A Dominant Mutation in the Stereocilia‐Expressing Gene TBC 1 D 24 is a Probable Cause for Nonsyndromic Hearing Impairment
Author(s) -
Zhang Luping,
Hu Lingxiang,
Chai Yongchuan,
Pang Xiuhong,
Yang Tao,
Wu Hao
Publication year - 2014
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.22558
Subject(s) - biology , genetics , stereocilia (inner ear) , mutation , cochlea , gene , neuroscience , hair cell
Mutations in TBC 1 D 24 have been linked to a variety of epileptic syndromes and recently to syndromic hearing impairment DOORS syndrome and nonsyndromic hearing impairment DFNB 86. All TBC 1 D 24 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 TBC 1 D 24 . Whole‐exome sequencing identified a heterozygous p.Ser178Leu variant of TBC 1 D 24 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 TBC 1 D 24 is a probable cause for dominant, nonsyndromic hearing impairment. Identification of TBC 1 D 24 as the stereocilia‐expressing gene may shed new light on its specific function in the inner ear.