title: TBC1D24 mutation causes autosomal-dominant nonsyndromic hearing loss.
abstract: Hereditary hearing loss is extremely heterogeneous. Over 70 genes have been identified to date, and with the advent of massively parallel sequencing, the pace of novel gene discovery has accelerated. In a family segregating progressive autosomal-dominant nonsyndromic hearing loss (NSHL), we used OtoSCOPE® to exclude mutations in known deafness genes and then performed segregation mapping and whole-exome sequencing to identify a unique variant, p.Ser178Leu, in TBC1D24 that segregates with the hearing loss phenotype. TBC1D24 encodes a GTPase-activating protein expressed in the cochlea. Ser178 is highly conserved across vertebrates and its change is predicted to be damaging. Other variants in TBC1D24 have been associated with a panoply of clinical symptoms including autosomal recessive NSHL, syndromic hearing impairment associated with onychodystrophy, osteodystrophy, mental retardation, and seizures (DOORS syndrome), and a wide range of epileptic disorders.
authors.affiliation: Molecular Otolaryngology & Renal Research Laboratories, Department of Otolaryngology-Head and Neck Surgery, University of Iowa Hospitals and Clinics, Iowa City, Iowa.
authors.forename: Hela
authors.initials: H
authors.lastname: Azaiez
authors.forename: Kevin T
authors.initials: KT
authors.lastname: Booth
authors.forename: Fengxiao
authors.initials: F
authors.lastname: Bu
authors.forename: Patrick
authors.initials: P
authors.lastname: Huygen
authors.forename: Seiji B
authors.initials: SB
authors.lastname: Shibata
authors.forename: A Eliot
authors.initials: AE
authors.lastname: Shearer
authors.forename: Diana
authors.initials: D
authors.lastname: Kolbe
authors.forename: Nicole
authors.initials: N
authors.lastname: Meyer
authors.forename: E Ann
authors.initials: EA
authors.lastname: Black-Ziegelbein
authors.forename: Richard J H
authors.initials: RJ
authors.lastname: Smith
mesh_terms: D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D003638:Deafness / Q000235:genetics; D059472:Exome; D005260:Female; D020690:GTPase-Activating Proteins; D015870:Gene Expression; D005799:Genes, Dominant; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009154:Mutation; D009419:Nerve Tissue Proteins; D010375:Pedigree; D016415:Sequence Alignment
chemical_list: D002352:Carrier Proteins; D020690:GTPase-Activating Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C552551:TBC1D24 protein, human
keywords: OtoSCOPE®; TBC1D24; autosomal dominant; hearing impairment; hearing loss; nonsyndromic; pleiotropy
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