{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T04:26:40Z","timestamp":1788323200093,"version":"build-2803163510"},"reference-count":52,"publisher":"National Academy of Sciences","issue":"26","license":[{"start":{"date-parts":[[2022,6,21]],"date-time":"2022-06-21T00:00:00Z","timestamp":1655769600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000055","name":"HHS | NIH | National Institute on Deafness and Other Communication Disorders","doi-asserted-by":"publisher","award":["R01DC009645"],"award-info":[{"award-number":["R01DC009645"]}],"id":[{"id":"10.13039\/100000055","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000055","name":"HHS | NIH | National Institute on Deafness and Other Communication Disorders","doi-asserted-by":"publisher","award":["R01DC012836"],"award-info":[{"award-number":["R01DC012836"]}],"id":[{"id":"10.13039\/100000055","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2022,6,28]]},"abstract":"<jats:p>\n                    Discovery of deafness genes and elucidating their functions have substantially contributed to our understanding of hearing physiology and its pathologies. Here we report on DNA variants in\n                    <jats:italic>MINAR2<\/jats:italic>\n                    , encoding membrane integral NOTCH2-associated receptor 2, in four families underlying autosomal recessive nonsyndromic deafness. Neurologic evaluation of affected individuals at ages ranging from 4 to 80 y old does not show additional abnormalities.\n                    <jats:italic>MINAR2<\/jats:italic>\n                    is a recently annotated gene with limited functional understanding. We detected three\n                    <jats:italic>MINAR2<\/jats:italic>\n                    variants, c.144G &gt; A (p.Trp48*), c.412_419delCGGTTTTG (p.Arg138Valfs*10), and c.393G &gt; T, in 13 individuals with congenital- or prelingual-onset severe-to-profound sensorineural hearing loss (HL). The c.393G &gt; T variant is shown to disrupt a splice donor site. We show that\n                    <jats:italic>Minar2<\/jats:italic>\n                    is expressed in the mouse inner ear, with the protein localizing mainly in the hair cells, spiral ganglia, the spiral limbus, and the stria vascularis. Mice with loss of function of the Minar2 protein (\n                    <jats:italic>\n                      Minar2\n                      <jats:sup>tm1b\/tm1b<\/jats:sup>\n                    <\/jats:italic>\n                    ) present with rapidly progressive sensorineural HL associated with a reduction in outer hair cell stereocilia in the shortest row and degeneration of hair cells at a later age. We conclude that MINAR2 is essential for hearing in humans and mice and its disruption leads to sensorineural HL. Progressive HL observed in mice and in some affected individuals and as well as relative preservation of hair cells provides an opportunity to interfere with HL using genetic therapies.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2204084119","type":"journal-article","created":{"date-parts":[[2022,6,21]],"date-time":"2022-06-21T15:03:30Z","timestamp":1655823810000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":9,"title":["Mutations in\n                    <i>MINAR2<\/i>\n                    encoding membrane integral NOTCH2-associated receptor 2 cause deafness in humans and mice"],"prefix":"10.1073","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4052-8833","authenticated-orcid":false,"given":"Guney","family":"Bademci","sequence":"first","affiliation":[{"name":"Dr. John T. 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Hussmann Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL 33136"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muzeyyen","family":"Yildirim Baylan","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Faculty of Medicine, Dicle University, Diyarbakir 21200, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0916-7347","authenticated-orcid":false,"given":"Neil J.","family":"Ingham","sequence":"additional","affiliation":[{"name":"Wolfson Centre for Age-Related Diseases, King\u2018s College London, London, SE1 1UL, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Chen","sequence":"additional","affiliation":[{"name":"Wolfson Centre for Age-Related Diseases, King\u2018s College London, London, SE1 1UL, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire J.","family":"Sineni","sequence":"additional","affiliation":[{"name":"John P. 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Hussmann Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL 33136"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7583-0349","authenticated-orcid":false,"given":"Duygu","family":"Duman","sequence":"additional","affiliation":[{"name":"Department of Audiology, Faculty of Health Sciences, Ankara University, Ankara 06100, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nitu","family":"Singh","sequence":"additional","affiliation":[{"name":"Oriental College of Pharmacy and Research, Oriental University, 453555 Indore, Madhya Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8968-2447","authenticated-orcid":false,"given":"Gaurav","family":"Harlalka","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Rajarshi Shahu College of Pharmacy, 443001 Malvihir, Buldana, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shirish P.","family":"Jain","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Rajarshi Shahu College of Pharmacy, 443001 Malvihir, Buldana, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3546-1726","authenticated-orcid":false,"given":"Barry A.","family":"Chioza","sequence":"additional","affiliation":[{"name":"College of Medicine and Health, University of Exeter Medical School, RD&amp;E NHS Foundation Trust, Exeter, EX2 5DW, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherina","family":"Walz","sequence":"additional","affiliation":[{"name":"Dr. John T. 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