{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T11:17:32Z","timestamp":1792495052720,"version":"4.5.0"},"reference-count":40,"publisher":"National Academy of Sciences","issue":"6","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2013,2,5]]},"abstract":"<jats:p>\n                    Age-related hearing loss and noise-induced hearing loss are major causes of human morbidity. Here we used genetics and functional studies to show that a shared cause of these disorders may be loss of function of the ATP-gated P2X\n                    <jats:sub>2<\/jats:sub>\n                    receptor (ligand-gated ion channel, purinergic receptor 2) that is expressed in sensory and supporting cells of the cochlea. Genomic analysis of dominantly inherited, progressive sensorineural hearing loss DFNA41 in a six-generation kindred revealed a rare heterozygous allele,\n                    <jats:italic>P2RX2 c.178G &gt; T<\/jats:italic>\n                    (p.V60L), at chr12:133,196,029, which cosegregated with fully penetrant hearing loss in the index family, and also appeared in a second family with the same phenotype. The mutation was absent from more than 7,000 controls. P2RX2 p.V60L abolishes two hallmark features of P2X\n                    <jats:sub>2<\/jats:sub>\n                    receptors: ATP-evoked inward current response and ATP-stimulated macropore permeability, measured as loss of ATP-activated FM1-43 fluorescence labeling. Coexpression of mutant and WT P2X\n                    <jats:sub>2<\/jats:sub>\n                    receptor subunits significantly reduced ATP-activated membrane permeability.\n                    <jats:italic>P2RX2<\/jats:italic>\n                    -null mice developed severe progressive hearing loss, and their early exposure to continuous moderate noise led to high-frequency hearing loss as young adults. Similarly, among family members heterozygous for P2RX2 p.V60L, noise exposure exacerbated high-frequency hearing loss in young adulthood. Our results suggest that P2X\n                    <jats:sub>2<\/jats:sub>\n                    function is required for life-long normal hearing and for protection from exposure to noise.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1222285110","type":"journal-article","created":{"date-parts":[[2013,1,24]],"date-time":"2013-01-24T05:03:36Z","timestamp":1359003816000},"page":"2228-2233","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":153,"title":["Mutation of the ATP-gated P2X\n                    <sub>2<\/sub>\n                    receptor leads to progressive hearing loss and increased susceptibility to noise"],"prefix":"10.1073","volume":"110","author":[{"given":"Denise","family":"Yan","sequence":"first","affiliation":[{"name":"Department of Otolaryngology, University of Miami School of Medicine, Miami, FL 33136;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, University of Kentucky Medical Center, Lexington, KY 40536;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"Walsh","sequence":"additional","affiliation":[{"name":"Department of Medicine and Department of Genome Sciences, University of Washington, Seattle, WA 98195;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dinghua","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology and Head-Neck Surgery, Second Xiangya Hospital of Central South University, Changsha 410011, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huijun","family":"Yuan","sequence":"additional","affiliation":[{"name":"Institute of Otolaryngology, Chinese PLA General Hospital, Beijing 100853, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asli","family":"Sirmaci","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, University of Miami School of Medicine, Miami, FL 33136;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taro","family":"Fujikawa","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Structure and Dynamics, Section on Structural Cell Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann Chi Yan","family":"Wong","sequence":"additional","affiliation":[{"name":"Translational Neuroscience Facility and Department of Physiology, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tze L.","family":"Loh","sequence":"additional","affiliation":[{"name":"Translational Neuroscience Facility and Department of Physiology, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilin","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, University of Miami School of Medicine, Miami, FL 33136;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u2019hamed","family":"Grati","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, University of Miami School of Medicine, Miami, FL 33136;"},{"name":"Laboratory of Cell Structure and Dynamics, Section on Structural Cell Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srdjan M.","family":"Vlajkovic","sequence":"additional","affiliation":[{"name":"Department of Physiology and Centre for Brain Research, School of Medical Sciences and Section of Audiology, School of Population Health, University of Auckland, Auckland, New Zealand;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Blanton","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, University of Miami School of Medicine, Miami, FL 33136;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allen F.","family":"Ryan","sequence":"additional","affiliation":[{"name":"Departments of Otolaryngology and Neurosciences, University of California at San Diego, La Jolla, CA 92093; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng-Yi","family":"Chen","sequence":"additional","affiliation":[{"name":"Eaton-Peabody Laboratory, Department of Otology and Laryngology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter R.","family":"Thorne","sequence":"additional","affiliation":[{"name":"Department of Physiology and Centre for Brain Research, School of Medical Sciences and Section of Audiology, School of Population Health, University of Auckland, Auckland, New Zealand;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bechara","family":"Kachar","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Structure and Dynamics, Section on Structural Cell Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustafa","family":"Tekin","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, University of Miami School of Medicine, Miami, FL 33136;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Bo","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, University of Kentucky Medical Center, Lexington, KY 40536;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary D.","family":"Housley","sequence":"additional","affiliation":[{"name":"Translational Neuroscience Facility and Department of Physiology, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary-Claire","family":"King","sequence":"additional","affiliation":[{"name":"Department of Medicine and Department of Genome Sciences, University of Washington, Seattle, WA 98195;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue Z.","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, University of Miami School of Medicine, Miami, FL 33136;"},{"name":"Department of Otolaryngology and Head-Neck Surgery, Second Xiangya Hospital of Central South University, Changsha 410011, China;"},{"name":"Department of Human Genetics, University of Miami School of Medicine, Miami, FL 33136;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2013,1,23]]},"reference":[{"key":"e_1_3_3_1_2","article-title":"Global and regional hearing impairment prevalence: An analysis of 42 studies in 29 countries","author":"Stevens G","year":"2011","unstructured":"G Stevens, et al., Global and regional hearing impairment prevalence: An analysis of 42 studies in 29 countries. 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