{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T22:26:33Z","timestamp":1787005593244,"version":"build-2736575974"},"reference-count":50,"publisher":"National Academy of Sciences","issue":"13","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2009,3,31]]},"abstract":"<jats:p>\n                    Deafness is the most common form of sensory impairment in humans and is frequently caused by single gene mutations. Interestingly, different mutations in a gene can cause syndromic and nonsyndromic forms of deafness, as well as progressive and age-related hearing loss. We provide here an explanation for the phenotypic variability associated with mutations in the cadherin 23 gene (\n                    <jats:italic>CDH23<\/jats:italic>\n                    ).\n                    <jats:italic>CDH23<\/jats:italic>\n                    null alleles cause deaf-blindness (Usher syndrome type 1D; USH1D), whereas missense mutations cause nonsyndromic deafness (DFNB12). In a forward genetic screen, we have identified\n                    <jats:italic>salsa<\/jats:italic>\n                    mice, which suffer from hearing loss due to a\n                    <jats:italic>Cdh23<\/jats:italic>\n                    missense mutation modeling DFNB12. In contrast to\n                    <jats:italic>waltzer<\/jats:italic>\n                    mice, which carry a CDH23 null allele mimicking USH1D, hair cell development is unaffected in\n                    <jats:italic>salsa<\/jats:italic>\n                    mice. Instead, tip links, which are thought to gate mechanotransduction channels in hair cells, are progressively lost. Our findings suggest that DFNB12 belongs to a new class of disorder that is caused by defects in tip links. We propose that mutations in other genes that cause USH1 and nonsyndromic deafness may also have distinct effects on hair cell development and function.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0900691106","type":"journal-article","created":{"date-parts":[[2009,3,6]],"date-time":"2009-03-06T20:59:00Z","timestamp":1236373140000},"page":"5252-5257","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":90,"title":["A mouse model for nonsyndromic deafness (DFNB12) links hearing loss to defects in tip links of mechanosensory hair cells"],"prefix":"10.1073","volume":"106","author":[{"given":"Martin","family":"Schwander","sequence":"first","affiliation":[{"name":"Department of Cell Biology and"},{"name":"Institute of Childhood and Neglected Disease, The Scripps Research Institute, La Jolla, CA 92037;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and"},{"name":"Institute of Childhood and Neglected Disease, The Scripps Research Institute, La Jolla, CA 92037;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Tokita","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Biology, National Institute of Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Lelli","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Virginia School of Medicine, Charlottesville, VA 22908; 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