Mutations in a new gene encoding a protein of the hair bundle cause non-syndromic deafness at the DFNB16 locus

Hearing impairment affects about 1 in 1,000 children at birth. Approximatel y 70 loci implicated in non-syndromic forms of deafness have been reported in humans and 24 causative genes have been identified(1) (see also http://w ww.uia.ac.be/dnalab/hhh). We report a mouse transcript, isolated by a candi date deafness gene approach, that is expressed almost exclusively in the in ner ear. Genomic analysis shows that the human ortholog STRC (so called owi ng 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 interru pted by a stop codon in exon 20. We have identified two frameshift mutation s and a large deletion in the copy containing 29 coding exons in two famili es affected by autosomal recessive non-syndromal sensorineural deafness lin ked to the DFNB16 locus. Stereocilin is made up of 1,809 amino acids, and c ontains a putative signal petide and several hydrophobic segments. Using im munohistolabeling, we demonstrate that, in the mouse inner ear,stereocilin is expressed only in the sensory hair cells and is associated with the ster eocilia, the stiff microvilli forming the structure for mechanoreception of sound stimulation.