{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:56:25Z","timestamp":1760144185184,"version":"build-2065373602"},"reference-count":43,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,3,29]],"date-time":"2024-03-29T00:00:00Z","timestamp":1711670400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Education","award":["2020R1F1A1065834","2020R1A2C3005787","HI21C1576","6-2021-0086"],"award-info":[{"award-number":["2020R1F1A1065834","2020R1A2C3005787","HI21C1576","6-2021-0086"]}]},{"name":"Korean Health Technology R&amp;D Project, Ministry of Health and Welfare, Republic of Korea","award":["2020R1F1A1065834","2020R1A2C3005787","HI21C1576","6-2021-0086"],"award-info":[{"award-number":["2020R1F1A1065834","2020R1A2C3005787","HI21C1576","6-2021-0086"]}]},{"DOI":"10.13039\/501100008005","name":"Yonsei University College of Medicine","doi-asserted-by":"publisher","award":["2020R1F1A1065834","2020R1A2C3005787","HI21C1576","6-2021-0086"],"award-info":[{"award-number":["2020R1F1A1065834","2020R1A2C3005787","HI21C1576","6-2021-0086"]}],"id":[{"id":"10.13039\/501100008005","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: The vestibular phenotypes of patients with genetic hearing loss are poorly understood. Methods: we performed genetic testing including exome sequencing and vestibular function tests to investigate vestibular phenotypes and functions in patients with genetic hearing loss. Results: Among 627 patients, 143 (22.8%) had vestibular symptoms. Genetic variations were confirmed in 45 (31.5%) of the 143 patients. Nineteen deafness genes were linked with vestibular symptoms; the most frequent genes in autosomal dominant and recessive individuals were COCH and SLC26A4, respectively. Vestibular symptoms were mostly of the vertigo type, recurrent, and persisted for hours in the genetically confirmed and unconfirmed groups. Decreased vestibular function in the caloric test, video head impulse test, cervical vestibular-evoked myogenic potential, and ocular vestibular-evoked myogenic potential was observed in 42.0%, 16.3%, 57.8%, and 85.0% of the patients, respectively. The caloric test revealed a significantly higher incidence of abnormal results in autosomal recessive individuals than in autosomal dominant individuals (p = 0.011). The genes, including SLC26A4, COCH, KCNQ4, MYH9, NLRP3, EYA4, MYO7A, MYO15A, and MYH9, were heterogeneously associated with abnormalities in the vestibular function test. Conclusions: In conclusion, diverse vestibular symptoms are commonly concomitant with genetic hearing loss and are easily overlooked.<\/jats:p>","DOI":"10.3390\/jcm13072001","type":"journal-article","created":{"date-parts":[[2024,3,31]],"date-time":"2024-03-31T13:32:56Z","timestamp":1711891976000},"page":"2001","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Characterization of Vestibular Phenotypes in Patients with Genetic Hearing Loss"],"prefix":"10.3390","volume":"13","author":[{"given":"Ji Hyuk","family":"Han","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seong Hoon","family":"Bae","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sun Young","family":"Joo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jung Ah","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Se Jin","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1147-1476","authenticated-orcid":false,"given":"Seung Hyun","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0084-0216","authenticated-orcid":false,"given":"Dongju","family":"Won","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8741-6177","authenticated-orcid":false,"given":"Heon Yung","family":"Gee","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jae Young","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1906-6969","authenticated-orcid":false,"given":"Jinsei","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sung Huhn","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Butcher, E., Dezateux, C., Cortina-Borja, M., and Knowles, R.L. (2019). Prevalence of permanent childhood hearing loss detected at the universal newborn hearing screen: Systematic review and meta-analysis. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0219600"},{"key":"ref_2","first-page":"351","article-title":"Progress in identifying infants with hearing loss\u2014United States, 2006\u20132012","volume":"64","author":"Williams","year":"2015","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"16094","DOI":"10.1038\/nrdp.2016.94","article-title":"Congenital hearing loss","volume":"3","author":"Korver","year":"2017","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2151","DOI":"10.1056\/NEJMra050700","article-title":"Newborn hearing screening\u2014A silent revolution","volume":"354","author":"Morton","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1016\/S0140-6736(05)71047-3","article-title":"Sensorineural hearing loss in children","volume":"365","author":"Smith","year":"2005","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1097\/WCO.0000000000000519","article-title":"Genetics of vestibular syndromes","volume":"31","year":"2018","journal-title":"Curr. Opin. Neurol."},{"key":"ref_7","unstructured":"(2023, October 13). Deafness Variation Database. Available online: http:\/\/deafnessvariationdatabase.org\/."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1016\/j.ajhg.2018.08.006","article-title":"Genomic Landscape and Mutational Signatures of Deafness-Associated Genes","volume":"103","author":"Azaiez","year":"2018","journal-title":"Am. J. Hum. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"51","DOI":"10.3233\/VES-2008-18105","article-title":"Vestibular function in families with inherited autosomal dominant hearing loss","volume":"18","author":"Street","year":"2008","journal-title":"J. Vestib. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"S54","DOI":"10.1007\/s00415-015-7903-4","article-title":"Vestibular compensation: The neuro-otologist\u2019s best friend","volume":"263","author":"Lacour","year":"2016","journal-title":"J. Neurol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1038\/sj.ejhg.5201043","article-title":"Mutations in the COCH gene are a frequent cause of autosomal dominant progressive cochleo-vestibular dysfunction, but not of Meniere\u2019s disease","volume":"11","author":"Usami","year":"2003","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.heares.2016.02.009","article-title":"Vestibular function is associated with residual low-frequency hearing loss in patients with bi-allelic mutations in the SLC26A4 gene","volume":"335","author":"Jung","year":"2016","journal-title":"Hear. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2993","DOI":"10.1007\/s00405-015-3885-1","article-title":"Distinct vestibular phenotypes in DFNA9 families with COCH variants","volume":"273","author":"Kim","year":"2016","journal-title":"Eur. Arch. Otorhinolaryngol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1002\/humu.22855","article-title":"Novel COCH p.V123E Mutation, Causative of DFNA9 Sensorineural Hearing Loss and Vestibular Disorder, Shows Impaired Cochlin Post-Translational Cleavage and Secretion","volume":"36","author":"Jung","year":"2015","journal-title":"Hum. Mutat."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1111\/cge.13868","article-title":"Vestibular phenotype-genotype correlation in a cohort of 90 patients with Usher syndrome","volume":"99","author":"Wafa","year":"2021","journal-title":"Clin. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"990","DOI":"10.3109\/00016481003596508","article-title":"Vestibular function of patients with profound deafness related to GJB2 mutation","volume":"130","author":"Kasai","year":"2010","journal-title":"Acta Otolaryngol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1097\/01.mao.0000185062.12458.87","article-title":"Audiometric, vestibular, and genetic aspects of a DFNA9 family with a G88E COCH mutation","volume":"26","author":"Kemperman","year":"2005","journal-title":"Otol. Neurotol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1002\/humu.22701","article-title":"Identification of pathogenic mechanisms of COCH mutations, abolished cochlin secretion, and intracellular aggregate formation: Genotype-phenotype correlations in DFNA9 deafness and vestibular disorder","volume":"35","author":"Bae","year":"2014","journal-title":"Hum. Mutat."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1038\/ejhg.2014.83","article-title":"Progressive hearing loss and vestibular dysfunction caused by a homozygous nonsense mutation in CLIC5","volume":"23","author":"Seco","year":"2015","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1080\/00016480701258739","article-title":"Clinical characteristics and genotype-phenotype correlation of hearing loss patients with SLC26A4 mutations","volume":"127","author":"Suzuki","year":"2007","journal-title":"Acta Otolaryngol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/s00415-018-8842-7","article-title":"Genetic contribution to vestibular diseases","volume":"265","year":"2018","journal-title":"J. Neurol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1097\/MAO.0000000000000238","article-title":"Auditory and vestibular phenotypes associated with GATA3 mutation","volume":"35","author":"Chien","year":"2014","journal-title":"Otol. Neurotol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"S45","DOI":"10.1007\/s00415-015-7988-9","article-title":"Genetics of vestibular disorders: Pathophysiological insights","volume":"263","author":"Frejo","year":"2016","journal-title":"J. Neurol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1002\/humu.20478","article-title":"Truncating mutation of the DFNB59 gene causes cochlear hearing impairment and central vestibular dysfunction","volume":"28","author":"Ebermann","year":"2007","journal-title":"Hum. Mutat."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1097\/00005537-200202000-00017","article-title":"Phenotype of DFNA11: A nonsyndromic hearing loss caused by a myosin VIIA mutation","volume":"112","author":"Tamagawa","year":"2002","journal-title":"Laryngoscope"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.ajhg.2009.12.017","article-title":"Homozygosity mapping reveals mutations of GRXCR1 as a cause of autosomal-recessive nonsyndromic hearing impairment","volume":"86","author":"Schraders","year":"2010","journal-title":"Am. J. Hum. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.1038\/s41431-018-0256-6","article-title":"Stereocilin gene variants associated with episodic vertigo: Expansion of the DFNB16 phenotype","volume":"26","author":"Frykholm","year":"2018","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"830","DOI":"10.3389\/fneur.2019.00830","article-title":"Postural Instability in Subjects With Usher Syndrome","volume":"10","author":"Caldani","year":"2019","journal-title":"Front. Neurol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"714543","DOI":"10.3389\/fneur.2021.714543","article-title":"Peripheral Vestibular Dysfunction Is a Common Occurrence in Children With Non-syndromic and Syndromic Genetic Hearing Loss","volume":"12","author":"Wang","year":"2021","journal-title":"Front. Neurol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1086\/341558","article-title":"CDH23 mutation and phenotype heterogeneity: A profile of 107 diverse families with Usher syndrome and nonsyndromic deafness","volume":"71","author":"Astuto","year":"2002","journal-title":"Am. J. Hum. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1002\/ajmg.a.33828","article-title":"Vestibular dysfunction in DFNB1 deafness","volume":"155","author":"Dodson","year":"2011","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3233\/VES-2009-0343","article-title":"Classification of vestibular symptoms: Towards an international classification of vestibular disorders","volume":"19","author":"Bisdorff","year":"2009","journal-title":"J. Vestib. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"45973","DOI":"10.1038\/srep45973","article-title":"Genetic Predisposition to Sporadic Congenital Hearing Loss in a Pediatric Population","volume":"7","author":"Jung","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1097\/AUD.0000000000000734","article-title":"Genetic Inheritance of Late-Onset, Down-Sloping Hearing Loss and Its Implications for Auditory Rehabilitation","volume":"41","author":"Song","year":"2020","journal-title":"Ear Hear."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1007\/s00439-021-02367-z","article-title":"Differential genetic diagnoses of adult post-lingual hearing loss according to the audiogram pattern and novel candidate gene evaluation","volume":"141","author":"Rim","year":"2022","journal-title":"Hum. Genet."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1002\/humu.23630","article-title":"Expert specification of the ACMG\/AMP variant interpretation guidelines for genetic hearing loss","volume":"39","author":"Oza","year":"2018","journal-title":"Hum. Mutat."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1055\/s-0038-1666815","article-title":"Epidemiology of Vestibular Impairments in a Pediatric Population","volume":"39","author":"Quarez","year":"2018","journal-title":"Semin. Hear."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Escalera-Balsera, A., Robles-Bolivar, P., Parra-Perez, A.M., Murillo-Cuesta, S., Chua, H.C., Rodriguez-de la Rosa, L., Contreras, J., Domarecka, E., Amor-Dorado, J.C., and Soto-Varela, A. (2024). A rare haplotype of the GJD3 gene segregating in familial Meniere Disease interferes with connexin assembly. medRxiv, 1.","DOI":"10.1101\/2024.01.16.24300842"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.1097\/AUD.0000000000000878","article-title":"Burden of Rare Variants in the OTOG Gene in Familial Meniere\u2019s Disease","volume":"41","author":"Aran","year":"2020","journal-title":"Ear Hear."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1016\/j.otc.2010.05.008","article-title":"Audiovestibular testing in patients with Meniere\u2019s disease","volume":"43","author":"Adams","year":"2010","journal-title":"Otolaryngol. Clin. N. Am."},{"key":"ref_41","unstructured":"Smith, R.J., Shearer, A.E., Hildebrand, M.S., and Van Camp, G. (1993). GeneReviews, University of Washington."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e829","DOI":"10.1002\/ctm2.829","article-title":"Defective \u03b1-tectorin may involve tectorial membrane in familial Meniere disease","volume":"12","author":"Aran","year":"2022","journal-title":"Clin. Transl. Med."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Velde, H.M., Huizenga, X.J., Yntema, H.G., Haer-Wigman, L., Beynon, A.J., Oostrik, J., Pegge, S.A., Kremer, H., Lanting, C.P., and Pennings, R.J. (2023). Genotype and Phenotype Analyses of a Novel WFS1 Variant (c. 2512C> T p.(Pro838Ser)) Associated with DFNA6\/14\/38. Genes, 14.","DOI":"10.3390\/genes14020457"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/7\/2001\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:21:02Z","timestamp":1760106062000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/7\/2001"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,29]]},"references-count":43,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["jcm13072001"],"URL":"https:\/\/doi.org\/10.3390\/jcm13072001","relation":{},"ISSN":["2077-0383"],"issn-type":[{"type":"electronic","value":"2077-0383"}],"subject":[],"published":{"date-parts":[[2024,3,29]]}}}