{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T18:25:45Z","timestamp":1792520745450,"version":"4.5.0"},"reference-count":48,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,9,21]],"date-time":"2025-09-21T00:00:00Z","timestamp":1758412800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001774","name":"University of Sydney","doi-asserted-by":"publisher","award":["K7013_B341"],"award-info":[{"award-number":["K7013_B341"]}],"id":[{"id":"10.13039\/501100001774","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI22\/01838"],"award-info":[{"award-number":["PI22\/01838"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MedComm"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Meniere disease (MD) is a chronic inner ear disorder with significant heritability. This study compares the burden of rare high\u2010 and moderate\u2010impact coding variants in an MD cohort to determine whether genetic burden in sporadic MD (SMD) overlaps familial MD (FMD), potentially revealing hidden inheritance in SMD. Exome sequencing identified rare variants in unrelated FMD (\n                    <jats:italic>N<\/jats:italic>\n                    \u00a0=\u00a093) and SMD (\n                    <jats:italic>N<\/jats:italic>\n                    \u00a0=\u00a0287) patients. Gene Burden Analysis (GBA) was performed, and candidate genes were prioritized using the number of variant carriers, inner\u2010ear expression, and hearing\/balance\u2010related phenotypic annotations. FMD patients showed higher accumulation of missense and loss\u2010of\u2010function variants than SMD, especially in genes linked to auditory and vestibular function. GBA identified 269 enriched genes in SMD, with 31 annotated for inner ear phenotypes, while FMD had 432 with 51 pinpointed. Sporadic and FMD overlapped in 28.1% of enriched genes, with\n                    <jats:italic>ADGRV1<\/jats:italic>\n                    ,\n                    <jats:italic>MEGF8<\/jats:italic>\n                    , and\n                    <jats:italic>MYO7A<\/jats:italic>\n                    most commonly shared. Auditory brainstem responses from knockout mouse models supported hearing loss of three novel MD candidate genes (\n                    <jats:italic>NIN<\/jats:italic>\n                    ,\n                    <jats:italic>CCDC88C<\/jats:italic>\n                    , and\n                    <jats:italic>ANKRD24<\/jats:italic>\n                    ), consistent with patient hearing profiles. In conclusion, SMD and FMD have a divergent genetic architecture. The enrichment of missense variants in stria vascularis and hair cell stereocilia genes supports distinct pathogenic mechanisms and a multiallelic\u2010recessive inheritance pattern in MD.\n                  <\/jats:p>","DOI":"10.1002\/mco2.70394","type":"journal-article","created":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T05:06:39Z","timestamp":1758517599000},"source":"Crossref","is-referenced-by-count":11,"title":["Different Contribution of Missense and Loss\u2010of\u2010Function Variants to the Genetic Structure of Familial and Sporadic Meniere Disease"],"prefix":"10.1002","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1208-8348","authenticated-orcid":false,"given":"Alberto M.","family":"Parra\u2010Perez","sequence":"first","affiliation":[{"name":"Otology and Neurotology Group CTS495 Division of Otolaryngology Department of Surgery Instituto De Investigaci\u00f3n Biosanitaria ibs.GRANADA Universidad De Granada  Granada Spain"},{"name":"Sensorineural Pathology Programme Centro De Investigaci\u00f3n Biom\u00e9dica En Red en Enfermedades Raras CIBERER  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6068-8965","authenticated-orcid":false,"given":"Alvaro","family":"Gallego\u2010Martinez","sequence":"additional","affiliation":[{"name":"Otology and Neurotology Group CTS495 Division of Otolaryngology Department of Surgery Instituto De Investigaci\u00f3n Biosanitaria ibs.GRANADA Universidad De Granada  Granada Spain"},{"name":"Sensorineural Pathology Programme Centro De Investigaci\u00f3n Biom\u00e9dica En Red en Enfermedades Raras CIBERER  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1027-8594","authenticated-orcid":false,"given":"Alba","family":"Escalera\u2010Balsera","sequence":"additional","affiliation":[{"name":"Otology and Neurotology Group CTS495 Division of Otolaryngology Department of Surgery Instituto De Investigaci\u00f3n Biosanitaria ibs.GRANADA Universidad De Granada  Granada Spain"},{"name":"Sensorineural Pathology Programme Centro De Investigaci\u00f3n Biom\u00e9dica En Red en Enfermedades Raras CIBERER  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1481-290X","authenticated-orcid":false,"given":"Paula","family":"Robles\u2010Bolivar","sequence":"additional","affiliation":[{"name":"Otology and Neurotology Group CTS495 Division of Otolaryngology Department of Surgery Instituto De Investigaci\u00f3n Biosanitaria ibs.GRANADA Universidad De Granada  Granada Spain"},{"name":"Sensorineural Pathology Programme Centro De Investigaci\u00f3n Biom\u00e9dica En Red en Enfermedades Raras CIBERER  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2722-4947","authenticated-orcid":false,"given":"Patricia","family":"Perez\u2010Carpena","sequence":"additional","affiliation":[{"name":"Otology and Neurotology Group CTS495 Division of Otolaryngology Department of Surgery Instituto De Investigaci\u00f3n Biosanitaria ibs.GRANADA Universidad De Granada  Granada Spain"},{"name":"Sensorineural Pathology Programme Centro De Investigaci\u00f3n Biom\u00e9dica En Red en Enfermedades Raras CIBERER  Madrid Spain"},{"name":"Deparment of Otolaryngology Instituto De Investigaci\u00f3n Biosanitaria ibs.GRANADA Hospital Universitario San Cecilio  Granada Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8583-1430","authenticated-orcid":false,"given":"Jose A.","family":"Lopez\u2010Escamez","sequence":"additional","affiliation":[{"name":"Otology and Neurotology Group CTS495 Division of Otolaryngology Department of Surgery Instituto De Investigaci\u00f3n Biosanitaria ibs.GRANADA Universidad De Granada  Granada Spain"},{"name":"Sensorineural Pathology Programme Centro De Investigaci\u00f3n Biom\u00e9dica En Red en Enfermedades Raras CIBERER  Madrid Spain"},{"name":"Meniere's Disease Neuroscience Research Program Faculty of Medicine &amp; Health School of Medical Sciences The Kolling Institute The University of Sydney  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,21]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3233\/VES-150549"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/MAO.0b013e3182868818"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2016.00182"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41435-024-00260-z"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12150"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0022215100130567"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/AUD.0000000000000878"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heares.2021.108329"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10162-023-00896-0"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.829"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2019.00076"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2019-106159"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10162-022-00880-0"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0975-20.2021"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2009.05.023"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12915-022-01349-5"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00438-015-0995-9"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-020-10278-8"},{"issue":"1","key":"e_1_2_11_20_1","first-page":"646","article-title":"The Genomic Landscape of M\u00e9ni\u00e8re's Disease: A Path to Endolymphatic Hydrops","volume":"25","author":"Fisch K. 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