{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T18:12:41Z","timestamp":1773339161632,"version":"3.50.1"},"reference-count":48,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,5,27]],"date-time":"2021-05-27T00:00:00Z","timestamp":1622073600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["17-15-01051"],"award-info":[{"award-number":["17-15-01051"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Hereditary nonsyndromic sensorineural hearing loss is a disease in which hearing loss occurs due to damage to the organ of the inner ear, the auditory nerve, or the center in the brain that is responsible for the perception of sound, characterized by wide locus and allelic heterogeneity and different types of inheritance. Given the diversity of population of the Russian Federation, it seems necessary to study the ethnic characteristics of the molecular causes of the disease. The aim is to study the molecular and genetic causes of hereditary sensorineural hearing loss in Chuvash, the fifth largest ethnic group in Russia. DNA samples of 26 patients from 21 unrelated Chuvash families from the Republic of Chuvashia, in whom the diagnosis of hereditary sensorineural hearing loss had been established, were analyzed using a combination of targeted Sanger sequencing, multiplex ligase-dependent probe amplification, and whole exome sequencing. The homozygous variant NM_133261.3(GIPC3):c.245A&gt;G (p.Asn82Ser) is the major molecular cause of hereditary sensorineural hearing loss in 23% of Chuvash patients (OMIM #601869). Its frequency was 25% in patients and 1.1% in healthy Chuvash population. Genotyping of the NM_133261.3(GIPC3):c.245A&gt;G (p.Asn82Ser) variant in five neighboring populations from the Volga-Ural region (Russian, Udmurt, Mary, Tatar, Bushkir) found no evidence that this variant is common in those populations.<\/jats:p>","DOI":"10.3390\/genes12060820","type":"journal-article","created":{"date-parts":[[2021,5,27]],"date-time":"2021-05-27T11:07:02Z","timestamp":1622113622000},"page":"820","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Genetic Variant c.245A&gt;G (p.Asn82Ser) in GIPC3 Gene Is a Frequent Cause of Hereditary Nonsyndromic Sensorineural Hearing Loss in Chuvash Population"],"prefix":"10.3390","volume":"12","author":[{"given":"Nika V.","family":"Petrova","sequence":"first","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0972-5118","authenticated-orcid":false,"given":"Andrey V.","family":"Marakhonov","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9493-6544","authenticated-orcid":false,"given":"Natalia V.","family":"Balinova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna V.","family":"Abrukova","sequence":"additional","affiliation":[{"name":"Presidential Perinatal Center of the Public Health Ministry of Chuvashia, Genetic Counseling Department, 428018 Cheboksary, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6414-436X","authenticated-orcid":false,"given":"Fedor A.","family":"Konovalov","sequence":"additional","affiliation":[{"name":"Independent Clinical Bioinformatics Laboratory, 123181 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergey I.","family":"Kutsev","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3586-3458","authenticated-orcid":false,"given":"Rena A.","family":"Zinchenko","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"},{"name":"N.A. Semashko National Research Institute of Public Health, 105064 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16094","DOI":"10.1038\/nrdp.2016.94","article-title":"Congenital hearing loss","volume":"12","author":"Korver","year":"2017","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"31","DOI":"10.17116\/otorino201883431","article-title":"Twenty years of clinical studies of GJB2-linked hearing loss in Russia","volume":"83","author":"Markova","year":"2018","journal-title":"Vestn. Otorinolaringol."},{"key":"ref_3","first-page":"671","article-title":"Genetics of human hereditary hearing impairment","volume":"29","author":"Meena","year":"2017","journal-title":"J. Ayub. Med. Coll. Abbottabad"},{"key":"ref_4","unstructured":"(2020, October 02). World Health Organization. Available online: https:\/\/www.who.int\/topics\/deafness\/ru\/."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/978-981-13-6123-4_5","article-title":"Diagnosis, Intervention, and Prevention of Genetic Hearing Loss","volume":"1130","author":"Yang","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_6","unstructured":"(2021, March 31). Online Mendelian Inheritance in Man, Available online: http:\/\/www.ncbi.nlm.nih.gov\/OMIM."},{"key":"ref_7","unstructured":"Shearer, A., Hildebrand, M.S., and Smith, R.J.H. (2020, October 02). Hereditary Hearing Loss and Deafness Overview, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK1434\/."},{"key":"ref_8","first-page":"758","article-title":"Nonsyndromic hearing impairment: Unparalleled heterogeneity","volume":"60","author":"Willems","year":"1997","journal-title":"Am. J. Hum. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1111\/j.1749-6632.1991.tb19572.x","article-title":"Genetic epidemiology of hearing impairment","volume":"630","author":"Morton","year":"1991","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1016\/S0140-6736(01)06186-4","article-title":"Advances in hereditary deafness","volume":"358","author":"Tekin","year":"2001","journal-title":"Lancet"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1083\/jcb.118.5.1213","article-title":"Transcriptional downregulation of gap-junction proteins blocks junctional communication in human mammary tumor cell lines","volume":"118","author":"Lee","year":"1992","journal-title":"J. Cell Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1097\/00125817-200207000-00004","article-title":"GJB2 (connexin 26) variants and nonsyndromic sensorineural hearing loss: A HuGE review","volume":"4","author":"Kenneson","year":"2002","journal-title":"Genet. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"E34","DOI":"10.1002\/lary.24332","article-title":"GJB2-associated hearing loss: Systematic review of worldwide prevalence, genotype, and auditory phenotype","volume":"124","author":"Chan","year":"2014","journal-title":"Laryngoscope"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1038\/jhg.2010.101","article-title":"Carrier frequency of GJB2 gene mutations c.35delG, c.235delC and c.167delT among the populations of Eurasia","volume":"55","author":"Dzhemileva","year":"2010","journal-title":"J. Hum. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1134\/S1022795407090104","article-title":"Prevalences of hereditary diseases in different populations of Russia","volume":"43","author":"Zinchenko","year":"2007","journal-title":"Russ. J. Genet."},{"key":"ref_16","first-page":"13","article-title":"Features of the diversity of hereditary diseases in different regions and multiethnic populations of the Russian Federation","volume":"19","author":"Zinchenko","year":"2020","journal-title":"Med. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Vasilyeva, T.A., Marakhonov, A.V., Voskresenskaya, A.A., Kadyshev, V.V., K\u00e4smann-Kellner, B., Pozdeyeva, N.A., Katargina, L.A., Kutsev, S.I., and Zinchenko, R.A. (2020). Analysis of Genotype\u2013Phenotype Correlations in Aniridia. J. Med. Genet.","DOI":"10.1136\/jmedgenet-2019-106172"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Petrova, N.V., Kashirskaya, N.Y., Vasilyeva, T.A., Kondratyeva, E.I., Zhekaite, E.K., Voronkova, A.Y., Sherman, V.D., Galkina, V.A., Ginter, E.K., and Kutsev, S.I. (2020). Analysis of CFTR Mutation Spectrum in Ethnic Russian Cystic Fibrosis Patients. Genes, 11.","DOI":"10.3390\/genes11050554"},{"key":"ref_19","first-page":"18","article-title":"Epidemiology study of hereditary deafness (nonsyndromal and syndromal) Chuvashia Republic","volume":"6","author":"Zinchenko","year":"2007","journal-title":"Med. Genet."},{"key":"ref_20","first-page":"19","article-title":"The frequency of GJB2 gene mutations in patients with hereditary non-syndromic sensoneural hearing loss in eight populations of Karachay-Cherkess Republic","volume":"16","author":"Petrina","year":"2017","journal-title":"Med. Genet."},{"key":"ref_21","first-page":"47","article-title":"Analysis of pedigrees with nonsyndromic sensorineural hearing loss in assortative marriages","volume":"17","author":"Petrina","year":"2018","journal-title":"Med. Genet."},{"key":"ref_22","first-page":"556","article-title":"Genetic epidemiological and medical genetic study of hereditary deafness in Rostov Oblast","volume":"4","author":"Shokarev","year":"2005","journal-title":"Med. Genet."},{"key":"ref_23","first-page":"28","article-title":"Hereditary hearing disorders in Kirov Oblast","volume":"2","author":"Sharonova","year":"2009","journal-title":"Yakut Med. J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1134\/S1022795412030131","article-title":"Hereditary Deafness in Kirov Oblast: Estimation of the Incidence Rate and DNA Diagnosis in Children","volume":"48","author":"Zinchenko","year":"2012","journal-title":"Russ. J. Genet."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1134\/S1022795418070165","article-title":"Diversity and prevalence of hereditary diseases among Nogais of the Karachay-Cherkess Republic","volume":"54","author":"Zinchenko","year":"2018","journal-title":"Russ. J. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"65","DOI":"10.17116\/otorino20208504165","article-title":"Description of a rare case of hereditary hearing loss with X-linked recessive type of inheritance associated with the POU3F4 gene in the Nogai family","volume":"85","author":"Petrina","year":"2020","journal-title":"Vestn. Otorhinolaryngol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Lozier, E.R., Konovalov, F.A., Kanivets, I.V., Pyankov, D.V., Koshkin, P.A., Baleva, L.S., Sipyagina, A.E., Yakusheva, E.N., Kuchina, A.E., and Korostelev, S.A. (2018). De novo nonsense mutation in WHSC1 (NSD2) in patient with intellectual disability and dysmorphic features. J. Hum. Genet.","DOI":"10.1038\/s10038-018-0464-5"},{"key":"ref_28","unstructured":"Zhivotovsky, L.A. (1991). Population-Based Biometrics, Nauka. (In Russian)."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1093\/biomet\/26.4.404","article-title":"The use of confidence or fiducial limits illustrated in the canse of the binomial","volume":"26","author":"Clopper","year":"1934","journal-title":"Biometrika"},{"key":"ref_30","unstructured":"(2021, March 31). The Genome Aggregation Database. Available online: http:\/\/gnomad.broadinstitute.org."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1038\/ncomms1200","article-title":"Gipc3 mutations associated with audiogenic seizures and sensorineural hearing loss in mouse and human","volume":"15","author":"Charizopoulou","year":"2011","journal-title":"Nat. Commun."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1007\/s00439-011-1018-5","article-title":"Mutations of GIPC3 cause nonsyndromic hearing loss DFNB72 but not DFNB81 that also maps to chromosome 19p","volume":"130","author":"Rehman","year":"2011","journal-title":"Hum. Genet."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.gene.2013.03.042","article-title":"Homozygosity mapping identifies a novel GIPC3 mutation causing congenital nonsyndromic hearing loss in a Saudi family","volume":"521","author":"Ramzan","year":"2013","journal-title":"Gene"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Diaz-Horta, O., Duman, D., Foster, J., S\u0131rmac\u0131, A., Gonzalez, M., Mahdieh, N., Fotouhi, N., Bonyadi, M., Cengiz, F.B., and Menendez, I. (2012). Whole-exome sequencing efficiently detects rare mutations in autosomal recessive nonsyndromic hearing loss. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0050628"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Sirmaci, A., Edwards, Y.J., Akay, H., and Tekin, M. (2012). Challenges in whole exome sequencing: An example from hereditary deafness. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0032000"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.ijporl.2018.01.006","article-title":"A novel missense mutation in GIPC3 causes sensorineural hearing loss in an Iranian family revealed by targeted next-generation sequencing","volume":"108","author":"Asgharzade","year":"2018","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e917","DOI":"10.1002\/mgg3.917","article-title":"Sequence variants in genes causing nonsyndromic hearing loss in a Pakistani cohort","volume":"7","author":"Ahmad","year":"2019","journal-title":"Mol. Genet. Genom. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1002\/mgg3.131","article-title":"Diversity of the causal genes in hearing impaired Algerian individuals identified by whole exome sequencing","volume":"3","author":"Bonnet","year":"2015","journal-title":"Mol. Genet. Genom. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e23544","DOI":"10.1002\/jcla.23544","article-title":"Identification of novel variants in Iranian consanguineous pedigrees with nonsyndromic hearing loss by next-generation sequencing","volume":"34","author":"Bitarafan","year":"2020","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1089\/gtmb.2020.0153","article-title":"Screening Consanguineous Families for Hearing Loss Using the MiamiOtoGenes Panel","volume":"24","author":"Yan","year":"2020","journal-title":"Genet. Test Mol. Biomark."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Zhou, Y., Tariq, M., He, S., Abdullah, U., Zhang, J., and Baig, S.M. (2020). Whole exome sequencing identified mutations causing hearing loss in five consanguineous Pakistani families. BMC Med. Genet., 21.","DOI":"10.1186\/s12881-020-01087-x"},{"key":"ref_42","unstructured":"Alekseev, V. (1974). The Geography of Human Races, Nauka. [1st ed.]."},{"key":"ref_43","unstructured":"Kuzeev, R. (1985). The Peoples of the Volga and Ural Regions, Nauka. [1st ed.]."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1038\/ejhg.2008.234","article-title":"Genetic analysis of autosomal recessive osteopetrosis in Chuvashiya: The unique splice site mutation in TCIRG1 gene spread by the founder effect","volume":"17","author":"Bliznetz","year":"2009","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_45","first-page":"31","article-title":"The age of Arg200Trp mutation in VHL gene, the cause of autosomal recessive erythrocytosis in Chuvashia","volume":"6","author":"Vasserman","year":"2007","journal-title":"Med. Genet."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1126\/science.1133276","article-title":"Human Hair Growth Deficiency Is Linked to a Genetic Defect in the Phospholipase Gene LIPH","volume":"314","author":"Kazantseva","year":"2006","journal-title":"Science"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1016\/j.jid.2016.01.037","article-title":"Autosomal Recessive Hypotrichosis with Woolly Hair Caused by a Mutation in the Keratin 25 Gene Expressed in Hair Follicles","volume":"136","author":"Zernov","year":"2016","journal-title":"J. Investig. Dermatol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1134\/S1022795412060166","article-title":"Mutation p.E92K is the Primary Cause of Cystic Fibrosis in Chuvashes","volume":"48","author":"Stepanova","year":"2012","journal-title":"Russ. J. Genet."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/12\/6\/820\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:08:45Z","timestamp":1760162925000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/12\/6\/820"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,27]]},"references-count":48,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,6]]}},"alternative-id":["genes12060820"],"URL":"https:\/\/doi.org\/10.3390\/genes12060820","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,27]]}}}