{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T11:20:12Z","timestamp":1790680812726,"version":"4.1.0"},"reference-count":51,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2020,6,23]],"date-time":"2020-06-23T00:00:00Z","timestamp":1592870400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100002583","name":"American Hearing Research Foundation","doi-asserted-by":"publisher","award":["1AHRF2017"],"award-info":[{"award-number":["1AHRF2017"]}],"id":[{"id":"10.13039\/100002583","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000055","name":"National Institute on Deafness and Other Communication Disorders","doi-asserted-by":"publisher","award":["R01 DC011651"],"award-info":[{"award-number":["R01 DC011651"]}],"id":[{"id":"10.13039\/100000055","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000055","name":"National Institute on Deafness and Other Communication Disorders","doi-asserted-by":"publisher","award":["R01 DC003594"],"award-info":[{"award-number":["R01 DC003594"]}],"id":[{"id":"10.13039\/100000055","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Congenital hearing impairment is a sensory disorder that is genetically highly heterogeneous. By performing exome sequencing in two families with congenital nonsyndromic profound sensorineural hearing loss (SNHL), we identified autosomal dominantly inherited missense variants [p.(Asn283Ser); p.(Thr116Ile)] in GREB1L, a neural crest regulatory molecule. The p.(Thr116Ile) variant was also associated with bilateral cochlear aplasia and cochlear nerve aplasia upon temporal bone imaging, an ultra-rare phenotype previously seen in patients with de novo GREB1L variants. An important role of GREB1L in normal ear development has also been demonstrated by greb1l\u2212\/\u2212 zebrafish, which show an abnormal sensory epithelia innervation. Last, we performed a review of all disease-associated variation described in GREB1L, as it has also been implicated in renal, bladder and genital malformations. We show that the spectrum of features associated with GREB1L is broad, variable and with a high level of reduced penetrance, which is typically characteristic of neurocristopathies. So far, seven GREB1L variants (14%) have been associated with ear-related abnormalities. In conclusion, these results show that autosomal dominantly inherited variants in GREB1L cause profound SNHL. Furthermore, we provide an overview of the phenotypic spectrum associated with GREB1L variants and strengthen the evidence of the involvement of GREB1L in human hearing.<\/jats:p>","DOI":"10.3390\/genes11060687","type":"journal-article","created":{"date-parts":[[2020,6,24]],"date-time":"2020-06-24T07:14:19Z","timestamp":1592982859000},"page":"687","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Autosomal Dominantly Inherited GREB1L Variants in Individuals with Profound Sensorineural Hearing Impairment"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7310-6082","authenticated-orcid":false,"given":"Isabelle","family":"Schrauwen","sequence":"first","affiliation":[{"name":"Center for Statistical Genetics, Sergievsky Center, Taub Institute for Alzheimer\u2019s Disease and the Aging Brain, and the Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0792-5773","authenticated-orcid":false,"given":"Khurram","family":"Liaqat","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2887-5485","authenticated-orcid":false,"given":"Isabelle","family":"Schatteman","sequence":"additional","affiliation":[{"name":"Department of ENT, St-Augustinus Hospital Antwerp, 2610 Antwerp, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thashi","family":"Bharadwaj","sequence":"additional","affiliation":[{"name":"Center for Statistical Genetics, Sergievsky Center, Taub Institute for Alzheimer\u2019s Disease and the Aging Brain, and the Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2339-3500","authenticated-orcid":false,"given":"Abdul","family":"Nasir","sequence":"additional","affiliation":[{"name":"Synthetic Protein Engineering Lab (SPEL), Department of Molecular Science and Technology, Ajou University, Suwon 443-749, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anushree","family":"Acharya","sequence":"additional","affiliation":[{"name":"Center for Statistical Genetics, Sergievsky Center, Taub Institute for Alzheimer\u2019s Disease and the Aging Brain, and the Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wasim","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy","family":"Van Camp","sequence":"additional","affiliation":[{"name":"Center of Medical Genetics, University of Antwerp &amp; Antwerp University Hospital, 2650 Antwerp, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne M.","family":"Leal","sequence":"additional","affiliation":[{"name":"Center for Statistical Genetics, Sergievsky Center, Taub Institute for Alzheimer\u2019s Disease and the Aging Brain, and the Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,23]]},"reference":[{"key":"ref_1","unstructured":"Adam, M.P., Ardinger, H.H., Pagon, R.A., Wallace, S.E., Bean, L.J., Stephens, K., and Amemiya, A. 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