{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T09:40:22Z","timestamp":1780652422080,"version":"3.54.1"},"reference-count":43,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,5,27]],"date-time":"2022-05-27T00:00:00Z","timestamp":1653609600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"National Science Centre","doi-asserted-by":"publisher","award":["2016\/22\/E\/NZ5\/00470"],"award-info":[{"award-number":["2016\/22\/E\/NZ5\/00470"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004281","name":"National Science Centre","doi-asserted-by":"publisher","award":["2017\/27\/N\/NZ5\/02369"],"award-info":[{"award-number":["2017\/27\/N\/NZ5\/02369"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hearing is an important human sense for communicating and connecting with others. Partial deafness (PD) is a common hearing problem, in which there is a down-sloping audiogram. In this study, we apply a practical system for classifying PD patients, used for treatment purposes, to distinguish two groups of patients: one with almost normal hearing thresholds at low frequencies (PDT-EC, n = 20), and a second group with poorer thresholds at those same low frequencies (PDT-EAS, n = 20). After performing comprehensive genetic testing with a panel of 237 genes, we found that genetic factors can explain a significant proportion of both PDT-EC and PDT-EAS hearing losses, accounting, respectively, for approx. one-fifth and one-half of all the cases in our cohort. Most of the causative variants were located in dominant and recessive genes previously linked to PD, but more than half of the variants were novel. Among the contributors to PDT-EC we identified OSBPL2 and SYNE4, two relatively new hereditary hearing loss genes with a low publication profile. Our study revealed that, for all PD patients, a postlingual hearing loss more severe in the low-frequency range is associated with a higher detection rate of causative variants. Isolating a genetic cause of PD is important in terms of prognosis, therapeutic effectiveness, and risk of recurrence.<\/jats:p>","DOI":"10.3390\/ijms23116029","type":"journal-article","created":{"date-parts":[[2022,5,28]],"date-time":"2022-05-28T01:40:45Z","timestamp":1653702045000},"page":"6029","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Searching for the Molecular Basis of Partial Deafness"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3454-8002","authenticated-orcid":false,"given":"Dominika","family":"Ozi\u0119b\u0142o","sequence":"first","affiliation":[{"name":"Department of Genetics, Institute of Physiology and Pathology of Hearing, 02-042 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3140-8821","authenticated-orcid":false,"given":"Natalia","family":"Ba\u0142dyga","sequence":"additional","affiliation":[{"name":"Department of Genetics, Institute of Physiology and Pathology of Hearing, 02-042 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3856-8377","authenticated-orcid":false,"given":"Marcin L.","family":"Leja","sequence":"additional","affiliation":[{"name":"Department of Genetics, Institute of Physiology and Pathology of Hearing, 02-042 Warsaw, Poland"},{"name":"Postgraduate School of Molecular Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7141-9851","authenticated-orcid":false,"given":"Henryk","family":"Skar\u017cy\u0144ski","sequence":"additional","affiliation":[{"name":"Oto-Rhino-Laryngology Surgery Clinic, Institute of Physiology and Pathology of Hearing, 02-042 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4216-9141","authenticated-orcid":false,"given":"Monika","family":"O\u0142dak","sequence":"additional","affiliation":[{"name":"Department of Genetics, Institute of Physiology and Pathology of Hearing, 02-042 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1080\/00016480600606632","article-title":"Partial deafness cochlear implantation provides benefit to a new population of individuals with hearing loss","volume":"126","author":"Skarzynski","year":"2006","journal-title":"Acta Otolaryngol."},{"key":"ref_2","first-page":"CR555","article-title":"Hearing preservation in partial deafness treatment","volume":"16","author":"Skarzynski","year":"2010","journal-title":"Med. Sci. Monit."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1159\/000064134","article-title":"Preservation of residual hearing in children and post-lingually deafened adults after cochlear implantation: An initial study","volume":"64","author":"Skarzynski","year":"2002","journal-title":"ORL J Otorhinolaryngol. Relat. Spec."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1159\/000027695","article-title":"Electric-acoustic stimulation of the auditory system. New technology for severe hearing loss","volume":"61","author":"Kiefer","year":"1999","journal-title":"ORL J. Otorhinolaryngol. Relat. Spec."},{"key":"ref_5","first-page":"183","article-title":"Cochlear implants: Selection criteria and shifting borders","volume":"52","author":"Lenarz","year":"1998","journal-title":"Acta Otorhinolaryngol. Belg."},{"key":"ref_6","first-page":"CS20","article-title":"A new method of partial deafness treatment","volume":"9","author":"Skarzynski","year":"2003","journal-title":"Med. Sci. Monit."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"S21","DOI":"10.1179\/1467010014Z.000000000170","article-title":"Long-term results of partial deafness treatment","volume":"15","author":"Skarzynski","year":"2014","journal-title":"Cochlear Implant. Int."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1896","DOI":"10.1016\/j.ijporl.2015.08.040","article-title":"Expanding pediatric cochlear implant candidacy: A case study of electro-natural stimulation (ENS) in partial deafness treatment","volume":"79","author":"Skarzynski","year":"2015","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1002\/ajmg.1320460504","article-title":"Genetic epidemiological studies of early-onset deafness in the U.S. school-age population","volume":"46","author":"Marazita","year":"1993","journal-title":"Am. J. Med. Genet."},{"key":"ref_10","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_11","doi-asserted-by":"crossref","first-page":"2614","DOI":"10.1038\/s41436-019-0563-5","article-title":"A proposal for comprehensive newborn hearing screening to improve identification of deaf and hard-of-hearing children","volume":"21","author":"Shearer","year":"2019","journal-title":"Genet. Med."},{"key":"ref_12","unstructured":"Shearer, A., Hildebrand, M., and Smith, R. (2022, March 01). Hereditary Hearing Loss and Deafness Overview, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK1434\/."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Ozieblo, D., Obrycka, A., Lorens, A., Skarzynski, H., and Oldak, M. (2020). Cochlear Implantation Outcome in Children with DFNB1 locus Pathogenic Variants. J. Clin. Med., 9.","DOI":"10.3390\/jcm9010228"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Wu, N., Husile, H., Yang, L., Cao, Y., Li, X., Huo, W., Bai, H., Liu, Y., and Wu, Q. (2019). A novel pathogenic variant in OSBPL2 linked to hereditary late-onset deafness in a Mongolian family. BMC Med. Genet., 20.","DOI":"10.1186\/s12881-019-0781-3"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1002\/humu.9272","article-title":"Impaired calmodulin binding of myosin-7A causes autosomal dominant hearing loss (DFNA11)","volume":"24","author":"Bolz","year":"2004","journal-title":"Hum. Mutat."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1086\/497996","article-title":"GJB2 mutations and degree of hearing loss: A multicenter study","volume":"77","author":"Snoeckx","year":"2005","journal-title":"Am. J. Hum. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1007\/s10038-004-0223-7","article-title":"Clinical features of patients with GJB2 (connexin 26) mutations: Severity of hearing loss is correlated with genotypes and protein expression patterns","volume":"50","author":"Oguchi","year":"2005","journal-title":"J. Hum. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Bae, J.W., Kim, D.B., Choi, J.Y., Park, H.J., Lee, J.D., Hur, D.G., Bae, S.H., Jung, D.J., Lee, S.H., and Kim, U.K. (2012). Molecular and clinical characterization of the variable phenotype in Korean families with hearing loss associated with the mitochondrial A1555G mutation. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0042463"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Kim, Y., Han, J.H., Yoo, H.S., and Choi, B.Y. (2022). Molecular aetiology of ski-slope hearing loss and audiological course of cochlear implantees. Eur. Arch. Otorhinolaryngol.","DOI":"10.1007\/s00405-022-07317-7"},{"key":"ref_20","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":"2021","journal-title":"Hum. Genet."},{"key":"ref_21","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_22","doi-asserted-by":"crossref","first-page":"4408","DOI":"10.1038\/s41598-019-40586-7","article-title":"Frequency and clinical features of hearing loss caused by STRC deletions","volume":"9","author":"Yokota","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Sugiyama, K., Moteki, H., Kitajiri, S.I., Kitano, T., Nishio, S.Y., Yamaguchi, T., Wakui, K., Abe, S., Ozaki, A., and Motegi, R. (2019). Mid-Frequency Hearing Loss Is Characteristic Clinical Feature of OTOA-Associated Hearing Loss. Genes, 10.","DOI":"10.3390\/genes10090715"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.heares.2019.01.003","article-title":"Hereditary hearing loss; about the known and the unknown","volume":"376","author":"Kremer","year":"2019","journal-title":"Hear. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1007\/s10162-011-0282-3","article-title":"Genotype-phenotype correlation in DFNB8\/10 families with TMPRSS3 mutations","volume":"12","author":"Weegerink","year":"2011","journal-title":"J. Assoc. Res. Otolaryngol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"193S","DOI":"10.1177\/0003489415575056","article-title":"The patients associated with TMPRSS3 mutations are good candidates for electric acoustic stimulation","volume":"124","author":"Miyagawa","year":"2015","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1111\/cge.13839","article-title":"Spectrum and frequencies of non GJB2 gene mutations in Czech patients with early non-syndromic hearing loss detected by gene panel NGS and whole-exome sequencing","volume":"98","author":"Meszarosova","year":"2020","journal-title":"Clin. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Garcia-Garcia, G., Berzal-Serrano, A., Garcia-Diaz, P., Villanova-Aparisi, R., Juarez-Rodriguez, S., de Paula-Vernetta, C., Cavalle-Garrido, L., Jaijo, T., Armengot-Carceller, M., and Millan, J.M. (2020). Improving the Management of Patients with Hearing Loss by the Implementation of an NGS Panel in Clinical Practice. Genes, 11.","DOI":"10.3390\/genes11121467"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Naito, T., Nishio, S.Y., Iwasa, Y., Yano, T., Kumakawa, K., Abe, S., Ishikawa, K., Kojima, H., Namba, A., and Oshikawa, C. (2013). Comprehensive genetic screening of KCNQ4 in a large autosomal dominant nonsyndromic hearing loss cohort: Genotype-phenotype correlations and a founder mutation. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0063231"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1007\/s00439-018-1965-1","article-title":"De novo and inherited loss-of-function variants of ATP2B2 are associated with rapidly progressive hearing impairment","volume":"138","author":"Smits","year":"2019","journal-title":"Hum. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1002\/ar.24360","article-title":"Cochlear Implantation From the Perspective of Genetic Background","volume":"303","author":"Usami","year":"2020","journal-title":"Anat. Rec."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"113","DOI":"10.21053\/ceo.2019.00990","article-title":"Severe or Profound Sensorineural Hearing Loss Caused by Novel USH2A Variants in Korea: Potential Genotype-Phenotype Correlation","volume":"13","author":"Lee","year":"2020","journal-title":"Clin. Exp. Otorhinolaryngol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1159\/000508434","article-title":"A New Pathogenic Variant in the TRIOBP Associated with Profound Deafness Is Remediable with Cochlear Implantation","volume":"26","author":"Tekin","year":"2021","journal-title":"Audiol. Neurootol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1136\/jmedgenet-2020-106892","article-title":"Congenital sensorineural hearing loss as the initial presentation of PTPN11-associated Noonan syndrome with multiple lentigines or Noonan syndrome: Clinical features and underlying mechanisms","volume":"58","author":"Gao","year":"2021","journal-title":"J. Med. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s13023-015-0238-5","article-title":"OSBPL2 encodes a protein of inner and outer hair cell stereocilia and is mutated in autosomal dominant hearing loss (DFNA67)","volume":"10","author":"Thoenes","year":"2015","journal-title":"Orphanet. J. Rare Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1038\/gim.2014.90","article-title":"Identification of OSBPL2 as a novel candidate gene for progressive nonsyndromic hearing loss by whole-exome sequencing","volume":"17","author":"Xing","year":"2015","journal-title":"Genet. Med."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Koh, Y.I., Oh, K.S., Kim, J.A., Noh, B., Choi, H.J., Joo, S.Y., Rim, J.H., Kim, H.Y., Kim, D.Y., and Yu, S. (2022). OSBPL2 mutations impair autophagy and lead to hearing loss, potentially remedied by rapamycin. Autophagy, 1\u201322.","DOI":"10.1080\/15548627.2022.2040891"},{"key":"ref_38","first-page":"740","article-title":"The LINC complex is essential for hearing","volume":"123","author":"Horn","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"196","DOI":"10.4274\/balkanmedj.2017.0946","article-title":"A Novel Variant in SYNE4 Confirms its Causative Role in Sensorineural Hearing Loss","volume":"35","author":"Masterson","year":"2018","journal-title":"Balk. Med. J."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Ozieblo, D., Pazik, J., Stepniak, I., Skarzynski, H., and Oldak, M. (2020). Two Novel Pathogenic Variants Confirm RMND1 Causative Role in Perrault Syndrome with Renal Involvement. Genes, 11.","DOI":"10.3390\/genes11091060"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"20","DOI":"10.12688\/wellcomeopenres.10069.1","article-title":"Accurate clinical detection of exon copy number variants in a targeted NGS panel using DECoN","volume":"1","author":"Fowler","year":"2016","journal-title":"Wellcome Open Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"ref_43","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."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/11\/6029\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:19:59Z","timestamp":1760138399000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/11\/6029"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,27]]},"references-count":43,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2022,6]]}},"alternative-id":["ijms23116029"],"URL":"https:\/\/doi.org\/10.3390\/ijms23116029","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,27]]}}}