title: Mutations in a new gene encoding a protein of the hair bundle cause non-syndromic deafness at the DFNB16 locus.
abstract: Hearing impairment affects about 1 in 1,000 children at birth. Approximately 70 loci implicated in non-syndromic forms of deafness have been reported in humans and 24 causative genes have been identified (see also http://www.uia.ac.be/dnalab/hhh). We report a mouse transcript, isolated by a candidate deafness gene approach, that is expressed almost exclusively in the inner ear. Genomic analysis shows that the human ortholog STRC (so called owing to the name we have given its protein-stereocilin), which is located on chromosome 15q15, contains 29 exons encompassing approximately 19 kb. STRC is tandemly duplicated, with the coding sequence of the second copy interrupted by a stop codon in exon 20. We have identified two frameshift mutations and a large deletion in the copy containing 29 coding exons in two families affected by autosomal recessive non-syndromal sensorineural deafness linked to the DFNB16 locus. Stereocilin is made up of 1,809 amino acids, and contains a putative signal petide and several hydrophobic segments. Using immunohistolabeling, we demonstrate that, in the mouse inner ear, stereocilin is expressed only in the sensory hair cells and is associated with the stereocilia, the stiff microvilli forming the structure for mechanoreception of sound stimulation.
authors.affiliation: Unité de Génétique des Déficits Sensoriels, CNRS URA 1968, Institut Pasteur, 25 rue du Dr. Roux, 75724 Paris cedex 15, France.
authors.forename: E
authors.initials: E
authors.lastname: Verpy
authors.forename: S
authors.initials: S
authors.lastname: Masmoudi
authors.forename: I
authors.initials: I
authors.lastname: Zwaenepoel
authors.forename: M
authors.initials: M
authors.lastname: Leibovici
authors.forename: T P
authors.initials: TP
authors.lastname: Hutchin
authors.forename: I
authors.initials: I
authors.lastname: Del Castillo
authors.forename: S
authors.initials: S
authors.lastname: Nouaille
authors.forename: S
authors.initials: S
authors.lastname: Blanchard
authors.forename: S
authors.initials: S
authors.lastname: Lainé
authors.forename: J L
authors.initials: JL
authors.lastname: Popot
authors.forename: F
authors.initials: F
authors.lastname: Moreno
authors.forename: R F
authors.initials: RF
authors.lastname: Mueller
authors.forename: C
authors.initials: C
authors.lastname: Petit
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002675:Child, Preschool; D002874:Chromosome Mapping; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D003001:Cloning, Molecular; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D020869:Gene Expression Profiling; D005819:Genetic Markers / Q000235:genetics; D006198:Hair Cells, Auditory / Q000378:metabolism*; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D011506:Proteins / Q000737:chemistry / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020080:Tandem Repeat Sequences / Q000235:genetics
chemical_list: D005819:Genetic Markers; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D011506:Proteins; D012333:RNA, Messenger; C499079:STRC protein, human; C440007:Strc protein, mouse