title: A dominant mutation in the stereocilia-expressing gene TBC1D24 is a probable cause for nonsyndromic hearing impairment.
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.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China; Department of Otolaryngology-Head and Neck Surgery, Affiliated Hospital of Nantong University, Jiangsu, China.
authors.forename: Luping
authors.initials: L
authors.lastname: Zhang
authors.forename: Lingxiang
authors.initials: L
authors.lastname: Hu
authors.forename: Yongchuan
authors.initials: Y
authors.lastname: Chai
authors.forename: Xiuhong
authors.initials: X
authors.lastname: Pang
authors.forename: Tao
authors.initials: T
authors.lastname: Yang
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D002648:Child; D004252:DNA Mutational Analysis; D003638:Deafness / Q000175:diagnosis / Q000235:genetics; D059472:Exome; D005260:Female; D020690:GTPase-Activating Proteins; D015870:Gene Expression; D005799:Genes, Dominant; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D009419:Nerve Tissue Proteins; D010375:Pedigree; D016415:Sequence Alignment; D059547:Stereocilia / Q000235:genetics*; D055815:Young Adult
chemical_list: D002352:Carrier Proteins; D020690:GTPase-Activating Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C552551:TBC1D24 protein, human
keywords: TBC1D24; autosomal dominant; hearing impairment; hearing loss; nonsyndromic; stereocilia