{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:29:23Z","timestamp":1785403763121,"version":"3.56.0"},"reference-count":46,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T00:00:00Z","timestamp":1780099200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["222294"],"award-info":[{"award-number":["222294"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"award":["222294"],"award-info":[{"award-number":["222294"]}],"id":[{"id":"https:\/\/ror.org\/01gavpb45","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Canadian Foundation of Innovation","award":["9384"],"award-info":[{"award-number":["9384"]}]},{"name":"Canadian Foundation of Innovation","award":["13120"],"award-info":[{"award-number":["13120"]}]},{"DOI":"10.13039\/100008762","name":"Genome Canada","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100008762","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/029s29983","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008762","name":"Genome Atlantic","doi-asserted-by":"publisher","award":["AMGGI"],"award-info":[{"award-number":["AMGGI"]}],"id":[{"id":"10.13039\/100008762","id-type":"DOI","asserted-by":"publisher"}]},{"award":["AMGGI"],"award-info":[{"award-number":["AMGGI"]}],"id":[{"id":"https:\/\/ror.org\/0249g7f28","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Town of Grand Falls-Windsor"},{"name":"Memorial University"},{"id":[{"id":"https:\/\/ror.org\/04haebc03","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014646","name":"Government of Newfoundland and Labrador","doi-asserted-by":"publisher","award":["Innovation Fund"],"award-info":[{"award-number":["Innovation Fund"]}],"id":[{"id":"10.13039\/501100014646","id-type":"DOI","asserted-by":"publisher"}]},{"award":["Innovation Fund"],"award-info":[{"award-number":["Innovation Fund"]}],"id":[{"id":"https:\/\/ror.org\/01jet5b79","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Otosclerosis is a common cause of conductive hearing loss thought to result from dysregulated bone remodeling in the embryonic tissues of the globuli interossei. Both familial and sporadic cases have been reported. To date, 10 published OTSC loci and four genes (FOXL1 (OTSC11), SMARCA4 (OTSC12), MEPE, SERPINF1) have been identified in autosomal dominant families. Using a combined genetic and genomics approach in five affected siblings, we identified a nonsense mutation in Karyopherin subunit \u03b17 (KPNA7, c.49C&gt;T, p.R17X), the newest of the importin-\u03b1 family of nuclear transporters. KPNA7 is a key maternal factor involved in the classical transport of NLS-containing cargo proteins, active during early embryonic cleavage events and zygotic genome activation. So far, 377 cargo proteins associated with KPNA7 have been identified. Recessive KPNA7 variants cause skeletal abnormalities, epilepsy, intellectual disabilities and preimplantation embryo arrest (PREMBA). A closer look at the OTSC genes reveals their involvement in endochondral ossification signaling pathways. We explore how KPNA7 haploinsufficiency in the embryonic tissues of the otic capsule may cause dysregulated bone remodeling. This study expands the phenotypic spectrum of KPNA7 and provides new insights into the pathobiology of otosclerosis.<\/jats:p>","DOI":"10.3390\/ijms27114985","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T12:45:08Z","timestamp":1780404308000},"page":"4985","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Heterozygous Nonsense Mutation in the Nuclear Transport Factor KPNA7, a Maternal Factor Active in Embryonic Tissues, Causes Autosomal Dominant Otosclerosis"],"prefix":"10.3390","volume":"27","author":[{"given":"Tammy","family":"Benteau","sequence":"first","affiliation":[{"name":"Division of Biomedical Science, Faculty of Medicine, Memorial University, St. John\u2019s, NL A1B 3V6, Canada"},{"name":"Centre for Translational Genomics, Craig L. Dobbin Genetics Research Centre, 300 Prince Philip Drive, St. John\u2019s, NL A1B 3V6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nelly","family":"Abdelfatah","sequence":"additional","affiliation":[{"name":"Division of Biomedical Science, Faculty of Medicine, Memorial University, St. John\u2019s, NL A1B 3V6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Griffin","sequence":"additional","affiliation":[{"name":"Division of Biomedical Science, Faculty of Medicine, Memorial University, St. John\u2019s, NL A1B 3V6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cindy","family":"Penney","sequence":"additional","affiliation":[{"name":"Division of Biomedical Science, Faculty of Medicine, Memorial University, St. John\u2019s, NL A1B 3V6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pingzhao","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Computer Science, Western University, London, ON N6G 2V4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan G.","family":"Stanton","sequence":"additional","affiliation":[{"name":"National Centre for Audiology & School of Communication Sciences and Disorders, Faculty of Health Sciences, Western University, London, ON N6G 1H1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangju","family":"Zhai","sequence":"additional","affiliation":[{"name":"Division of Biomedical Science, Faculty of Medicine, Memorial University, St. John\u2019s, NL A1B 3V6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4032-0730","authenticated-orcid":false,"given":"Maxime","family":"Maheu","sequence":"additional","affiliation":[{"name":"\u00c9cole d\u2019Orthophonie et d\u2019Audiologie, Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, QC H3C 3J7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Curtis R.","family":"French","sequence":"additional","affiliation":[{"name":"Division of Biomedical Science, Faculty of Medicine, Memorial University, St. John\u2019s, NL A1B 3V6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4673-6470","authenticated-orcid":false,"given":"Terry-Lynn","family":"Young","sequence":"additional","affiliation":[{"name":"Division of Biomedical Science, Faculty of Medicine, Memorial University, St. John\u2019s, NL A1B 3V6, Canada"},{"name":"Centre for Translational Genomics, Craig L. Dobbin Genetics Research Centre, 300 Prince Philip Drive, St. John\u2019s, NL A1B 3V6, Canada"},{"name":"National Centre for Audiology & School of Communication Sciences and Disorders, Faculty of Health Sciences, Western University, London, ON N6G 1H1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,30]]},"reference":[{"key":"ref_1","first-page":"e241839","article-title":"Proceedings of the Round Table Discussion on the Fifth International Symposium on Otosclerosis and Stapes Surgery","volume":"21","author":"Orhan","year":"2025","journal-title":"J. Int. Adv. Otol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.14639\/0392-100X-suppl.1_3-45-2025-A1334","article-title":"Exploring the genetic landscape of otosclerosis: Current understanding and future perspectives","volume":"45","author":"Capobianco","year":"2025","journal-title":"Acta Otorhinolaryngol. 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