vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/vjgb-25-17vavilov-4486Research ArticleБИОТЕХНОЛОГИЯ В ПОСТГЕНОМНУЮ ЭРУMEDICAL GENETICSСравнительный анализ гаплотипов, несущих патогенные варианты c.1545T>G, c.2027T>A и c.919-2A>G гена SLC26A4, у пациентов с потерей слуха из Республики Тыва (Южная Сибирь)Comparative analysis of haplotypes carrying pathogenic variants c.1545T>G, c.2027T>A and c.919-2A>G of the SLC26A4 gene in patients with hearing loss from the Tyva Republic (Southern Siberia)https://orcid.org/0000-0001-5658-5974ДанильченкоВ. Ю.DanilchenkoV. Yu.

Новосибирск

Novosibirsk

https://orcid.org/0000-0003-1219-9881ЗыцарьМ. В.ZytsarM. V.

Новосибирск

Novosibirsk

https://orcid.org/0009-0007-5815-2807ПанинаЕ. А.PaninaE. A.

Новосибирск

Novosibirsk

https://orcid.org/0000-0001-9718-9038ОрищенкоК. Е.OrishchenkoK. E.

Новосибирск

Novosibirsk

https://orcid.org/0000-0003-1352-3591ПосухО. Л.PosukhO. L.

Новосибирск

Novosibirsk

posukh@bionet.nsc.ruФедеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук; Новосибирский национальный исследовательский государственный университетРоссияInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Novosibirsk State UniversityRussian Federation202504032025291144152Copyright © Данильченко В.Ю., Зыцарь М.В., Панина Е.А., Орищенко К.Е., Посух О.Л., 20252025Данильченко В.Ю., Зыцарь М.В., Панина Е.А., Орищенко К.Е., Посух О.Л.Danilchenko V.Y., Zytsar M.V., Panina E.A., Orishchenko K.E., Posukh O.L.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/4486

   Патогенные варианты в гене SLC26A4 (OMIM #605646), приводящие к несиндромальной рецессивно наследуемой потере слуха 4-го типа (DFNB4) и синдрому Пендреда, вносят весомый вклад в этиологию потери слуха во многих популяциях мира. Спектр и распространенность различных патогенных вариантов гена SLC26A4 характеризуются широкой этногеографической вариабельностью. Высокая частота некоторых из них в отдельных регионах мира может свидетельствовать об их независимом возникновении или же быть следствием эффекта основателя. Доля SLC26A4-ассоциированной потери слуха у тувинских пациентов (Республика Тыва, Южная Сибирь) является одной из самых высоких в мире (28.2 %). Подавляющее большинство мутантных SLC26A4-аллелей представлено тремя патогенными вариантами – c.919-2A>G, c.2027T>A и c.1545T>G (69.3, 17.5 и 8.0 % соответственно). Суммарная частота их гетерозиготного носительства в тувинской популяции достигает 7.1 %. Накопление этих вариантов у тувинских пациентов позволяет предположить роль эффекта основателя в их распространенности на территории Тувы, что может быть подтверждено общностью генетического окружения (гаплотипов) для каждого из них. Для реконструкции гаплотипов у носителей вариантов c.1545T>G и c.2027T>A были использованы данные генотипирования панели полиморфных генетических маркеров: пяти STR-маркеров (четыре из них фланкируют на разном расстоянии ген SLC26A4 и один является внутригенным) и девяти внутригенных SNP-маркеров. Сравнительный анализ реконструированных гаплотипов для c.1545T>G и c.2027T>A с ранее полученными данными о гаплотипах для c.919-2A>G показал, что каждый из анализируемых вариантов имеет особое и сходное для всех носителей того или иного варианта генетическое окружение, по-видимому, унаследованное от различных «предков-основателей». Эти данные подтверждают роль кумулятивного эффекта основателя в распространенности патогенных вариантов с.1545T>G, c.2027T>A и c.919-2A>G гена SLC26A4 у коренного населения Республики Тыва. Полученные данные актуальны как для прогнозирования распространенности SLC26A4-обусловленной потери слуха, так и для создания регион-специфичной ДНК-диагностики наследуемой потери слуха в Республике Тыва.

   Pathogenic variants in the SLC26A4 gene (OMIM #605646), leading to non-syndromic recessive hearing loss type 4 (DFNB4) and Pendred syndrome, significantly contribute to the etiology of hearing loss in many populations of the world. The spectrum and prevalence of different pathogenic SLC26A4 variants are characterized by wide ethno-geographical variability. A high frequency of some of them in certain regions of the world may indicate either their independent origin or be a consequence of the founder effect. The proportion of SLC26A4-associated hearing loss in Tuvinian patients (the Tyva Republic, Southern Siberia) is one of the highest in the world (28.2 %) and the vast majority of mutant SLC26A4 alleles are represented by three pathogenic variants c.919-2A>G, c.2027T>A and c.1545T>G (69.3, 17.5 and 8.0 %, respectively). Their overall carrier frequency in the Tuvinian population reaches 7.1 %. The accumulation of these variants in Tuvinian patients suggests a role of the founder effect in their prevalence in Tuva, which can be confirmed by the common genetic background (haplotypes) for each of them. For reconstruction of haplotypes in the carriers of variants c.1545T>G and c.2027T>A, the genotyping data of a panel of polymorphic genetic markers were used: five STRs (four of them flank the SLC26A4 gene at different distances and one is intragenic) and nine intragenic SNPs. Comparative analysis of the reconstructed haplotypes for c.1545T>G and c.2027T>A with previously obtained data on haplotypes for the c.919-2A>G variant showed that each of the analyzed variants has a specific (similar for all carriers of a particular variant) genetic background, apparently inherited from different “founder ancestors”. These data confirm the cumulative founder effect in the prevalence of pathogenic variants c.1545T>G, c.2027T>A, and c.919- 2A>G of the SLC26A4 gene in the indigenous population of the Tyva Republic. The obtained data are relevant both for predicting the prevalence of SLC26A4-caused hearing loss and for development of region-specific DNA diagnostics of inherited hearing loss in the Tyva Republic.

потеря слухаSLC26A4патогенные вариантыSTRSNPгаплотипыэффект основателяпопуляции Сибириhearing lossSLC26A4pathogenic variantsSTRsSNPshaplotypesfounder effectSiberian populationsИсследование выполнено при финансовой поддержке бюджетного проекта FWNR-2022-0021 Института цитологии и генетики СО РАН и гранта Министерства науки и высшего образования РФ FSUS-2024-0018.The study was carried out with the financial support of the budget project FWNR-2022-0021 of the Institute of Cytology and Genetics SB RAS and the grant FSUS-2024-0018 of the Ministry of Science and Higher Education of the Russian FederationReferencesAlbert S., Blons H., Jonard L., Feldmann D., Chauvin P., Loundon N., Sergent­Allaoui A., Houang M., Joannard A., Schmerber S., Delobel B., Leman J., Journel H., Catros H., Dollfus H., Eliot M.M., David A., Calais C., Drouin­Garraud V., Obstoy M.F., Tran Ba Huy P., Lacombe D., Duriez F., Francannet C., Bitoun P., Petit C., Garabédian E.N., Couderc R., Marlin S., Denoyelle F. SLC26A4 gene is frequently involved in nonsyndromic hearing impairment with enlarged vestibular aqueduct in Caucasian populations. Eur J Hum Genet. 2006;14(6):773­779. doi: 10.1038/sj.ejhg.5201611Albert S., Blons H., Jonard L., Feldmann D., Chauvin P., Loundon N., Sergent­Allaoui A., Houang M., Joannard A., Schmerber S., Delobel B., Leman J., Journel H., Catros H., Dollfus H., Eliot M.M., David A., Calais C., Drouin­Garraud V., Obstoy M.F., Tran Ba Huy P., Lacombe D., Duriez F., Francannet C., Bitoun P., Petit C., Garabédian E.N., Couderc R., Marlin S., Denoyelle F. SLC26A4 gene is frequently involved in nonsyndromic hearing impairment with enlarged vestibular aqueduct in Caucasian populations. Eur J Hum Genet. 2006;14(6):773­779. doi: 10.1038/sj.ejhg.5201611Ben Arab S., Masmoudi S., Beltaief N., Hachicha S., Ayadi H. Consanguinity and endogamy in Northern Tunisia and its impact on non-syndromic deafness. Genet Epidemiol. 2004;27(1):74-79. doi: 10.1002/gepi.10321Ben Arab S., Masmoudi S., Beltaief N., Hachicha S., Ayadi H. Consanguinity and endogamy in Northern Tunisia and its impact on non-syndromic deafness. Genet Epidemiol. 2004;27(1):74-79. doi: 10.1002/gepi.10321Bengtsson B.O., Thomson G. Measuring the strength of associations between HLA antigens and diseases. Tissue Antigens. 1981;18(5): 356­363. doi: 10.1111/j.1399­0039.1981.tb01404.xBengtsson B.O., Thomson G. Measuring the strength of associations between HLA antigens and diseases. Tissue Antigens. 1981;18(5): 356­363. doi: 10.1111/j.1399­0039.1981.tb01404.xChai Y., Huang Z., Tao Z., Li X., Li L., Li Y., Wu H., Yang T. Molecular etiology of hearing impairment associated with nonsyndromic enlarged vestibular aqueduct in East China. Am J Med Genet A. 2013;161A(9):2226­2233. doi: 10.1002/ajmg.a.36068Chai Y., Huang Z., Tao Z., Li X., Li L., Li Y., Wu H., Yang T. Molecular etiology of hearing impairment associated with nonsyndromic enlarged vestibular aqueduct in East China. Am J Med Genet A. 2013;161A(9):2226­2233. doi: 10.1002/ajmg.a.36068Chen Z., Zhang Y., Fan A., Zhang Y., Wu Y., Zhao Q., Zhou Y., Zhou C., Bawudong M., Mao X., Ma Y., Yang L., Ding Y., Wang X., Rao S. Brief communication: Y­chromosome haplogroup analysis indicates that Chinese Tuvans share distinctive affinity with Siberian Tuvans. Am J Phys Anthropol. 2011;144(3):492-497. doi: 10.1002/ajpa.21453Chen Z., Zhang Y., Fan A., Zhang Y., Wu Y., Zhao Q., Zhou Y., Zhou C., Bawudong M., Mao X., Ma Y., Yang L., Ding Y., Wang X., Rao S. Brief communication: Y­chromosome haplogroup analysis indicates that Chinese Tuvans share distinctive affinity with Siberian Tuvans. Am J Phys Anthropol. 2011;144(3):492-497. doi: 10.1002/ajpa.21453Choi B.Y., Stewart A.K., Nishimura K.K., Cha W.J., Seong M.W., Park S.S., Kim S.W., Chun Y.S., Chung J.W., Park S.N., Chang S.O., Kim C.S., Alper S.L., Griffith A.J., Oh S.H. Efficient molecular genetic diagnosis of enlarged vestibular aqueducts in East Asians. Genet Test Mol Biomarkers. 2009;13(5):679­687. doi: 10.1089/gtmb.2009.0054Choi B.Y., Stewart A.K., Nishimura K.K., Cha W.J., Seong M.W., Park S.S., Kim S.W., Chun Y.S., Chung J.W., Park S.N., Chang S.O., Kim C.S., Alper S.L., Griffith A.J., Oh S.H. Efficient molecular genetic diagnosis of enlarged vestibular aqueducts in East Asians. Genet Test Mol Biomarkers. 2009;13(5):679­687. doi: 10.1089/gtmb.2009.0054Chong J.X., Ouwenga R., Anderson R.L., Waggoner D.J., Ober C. A population-based study of autosomal-recessive disease-causing mutations in a founder population. Am J Hum Genet. 2012;91(4): 608­620. doi: 10.1016/j.ajhg.2012.08.007Chong J.X., Ouwenga R., Anderson R.L., Waggoner D.J., Ober C. A population-based study of autosomal-recessive disease-causing mutations in a founder population. Am J Hum Genet. 2012;91(4): 608­620. doi: 10.1016/j.ajhg.2012.08.007Common J.E., Di W.L., Davies D., Kelsell D.P. Further evidence for heterozygote advantage of GJB2 deafness mutations: a link with cell survival. J Med Genet. 2004;41(7):573­575. doi: 10.1136/jmg.2003.017632Common J.E., Di W.L., Davies D., Kelsell D.P. Further evidence for heterozygote advantage of GJB2 deafness mutations: a link with cell survival. J Med Genet. 2004;41(7):573­575. doi: 10.1136/jmg.2003.017632Dai P., Li Q., Huang D., Yuan Y., Kang D., Miller D.T., Shao H., Zhu Q., He J., Yu F., Liu X., Han B., Yuan H., Platt O.S., Han D., Wu B.L. SLC26A4 c.919-2A>G varies among Chinese ethnic groups as a cause of hearing loss. Genet Med. 2008;10(8):586­592. doi: 10.1097/gim.0b013e31817d2ef1Dai P., Li Q., Huang D., Yuan Y., Kang D., Miller D.T., Shao H., Zhu Q., He J., Yu F., Liu X., Han B., Yuan H., Platt O.S., Han D., Wu B.L. SLC26A4 c.919-2A>G varies among Chinese ethnic groups as a cause of hearing loss. Genet Med. 2008;10(8):586­592. doi: 10.1097/gim.0b013e31817d2ef1Danilchenko V.Y., Zytsar M.V., Maslova E.A., Bady­Khoo M.S., Barashkov N.A., Morozov I.V., Bondar A.A., Posukh O.L. Different rates of the SLC26A4-related hearing loss in two indigenous peoples of southern Siberia (Russia). Diagnostics (Basel). 2021;11(12): 2378. doi: 10.3390/diagnostics11122378Danilchenko V.Y., Zytsar M.V., Maslova E.A., Bady­Khoo M.S., Barashkov N.A., Morozov I.V., Bondar A.A., Posukh O.L. Different rates of the SLC26A4-related hearing loss in two indigenous peoples of southern Siberia (Russia). Diagnostics (Basel). 2021;11(12): 2378. doi: 10.3390/diagnostics11122378Danilchenko V.Y., Zytsar M.V., Maslova E.A., Orishchenko K.E., Posukh O.L. Insight into the natural history of pathogenic variant c.919-2A>G in the SLC26A4 gene involved in hearing loss: the evidence for its common origin in southern Siberia (Russia). Genes (Basel). 2023;14(4):928. doi: 10.3390/genes14040928Danilchenko V.Y., Zytsar M.V., Maslova E.A., Orishchenko K.E., Posukh O.L. Insight into the natural history of pathogenic variant c.919-2A>G in the SLC26A4 gene involved in hearing loss: the evidence for its common origin in southern Siberia (Russia). Genes (Basel). 2023;14(4):928. doi: 10.3390/genes14040928Du W., Guo Y., Wang C., Wang Y., Liu X. A systematic review and meta-analysis of common mutations of SLC26A4 gene in Asian populations. Int J Pediatr Otorhinolaryngol. 2013;77(10):1670-1676. doi: 10.1016/j.ijporl.2013.07.023Du W., Guo Y., Wang C., Wang Y., Liu X. A systematic review and meta-analysis of common mutations of SLC26A4 gene in Asian populations. Int J Pediatr Otorhinolaryngol. 2013;77(10):1670-1676. doi: 10.1016/j.ijporl.2013.07.023Erdenechuluun J., Lin Y.H., Ganbat K., Bataakhuu D., Makhbal Z., Tsai C.Y., Lin Y.H., Chan Y.H., Hsu C.J., Hsu W.C., Chen P.L., Wu C.C. Unique spectra of deafness-associated mutations in Mongolians provide insights into the genetic relationships among Eurasian populations. PLoS One. 2018;13(12):e0209797. doi: 10.1371/journal.pone.0209797Erdenechuluun J., Lin Y.H., Ganbat K., Bataakhuu D., Makhbal Z., Tsai C.Y., Lin Y.H., Chan Y.H., Hsu C.J., Hsu W.C., Chen P.L., Wu C.C. Unique spectra of deafness-associated mutations in Mongolians provide insights into the genetic relationships among Eurasian populations. PLoS One. 2018;13(12):e0209797. doi: 10.1371/journal.pone.0209797Gillam M.P., Sidhaye A.R., Lee E.J., Rutishauser J., Stephan C.W., Kopp P. Functional characterization of pendrin in a polarized cell system. Evidence for pendrin­mediated apical iodide efflux. J Biol Chem. 2004;279(13):13004­13010. doi: 10.1074/jbc.M313648200Gillam M.P., Sidhaye A.R., Lee E.J., Rutishauser J., Stephan C.W., Kopp P. Functional characterization of pendrin in a polarized cell system. Evidence for pendrin­mediated apical iodide efflux. J Biol Chem. 2004;279(13):13004­13010. doi: 10.1074/jbc.M313648200Huang S., Han D., Yuan Y., Wang G., Kang D., Zhang X., Yan X., Meng X., Dong M., Dai P. Extremely discrepant mutation spectrum of SLC26A4 between Chinese patients with isolated Mondini deformity and enlarged vestibular aqueduct. J Transl Med. 2011;9:167. doi: 10.1186/1479­5876­9­167Huang S., Han D., Yuan Y., Wang G., Kang D., Zhang X., Yan X., Meng X., Dong M., Dai P. Extremely discrepant mutation spectrum of SLC26A4 between Chinese patients with isolated Mondini deformity and enlarged vestibular aqueduct. J Transl Med. 2011;9:167. doi: 10.1186/1479­5876­9­167Kun L., Jiexiang H., Hua L., Junlin H., Yijun R., Lixian Z., Mingqiao C. Genetic screening of 15 hearing loss variants in 77,647 neonates with clinical follow-up. Mol Genet Genomic Med. 2024;12(1): e2324. doi: 10.1002/mgg3.2324Kun L., Jiexiang H., Hua L., Junlin H., Yijun R., Lixian Z., Mingqiao C. Genetic screening of 15 hearing loss variants in 77,647 neonates with clinical follow-up. Mol Genet Genomic Med. 2024;12(1): e2324. doi: 10.1002/mgg3.2324Lu Y.C., Wu C.C., Shen W.S., Yang T.H., Yeh T.H., Chen P.J., Yu I.S., Lin S.W., Wong J.M., Chang Q., Lin X., Hsu C.J. Establishment of a knock-in mouse model with the SLC26A4 c.919-2A>G mutation and characterization of its pathology. PLoS One. 2011;6(7):e22150. doi: 10.1371/journal.pone.0022150Lu Y.C., Wu C.C., Shen W.S., Yang T.H., Yeh T.H., Chen P.J., Yu I.S., Lin S.W., Wong J.M., Chang Q., Lin X., Hsu C.J. Establishment of a knock-in mouse model with the SLC26A4 c.919-2A>G mutation and characterization of its pathology. PLoS One. 2011;6(7):e22150. doi: 10.1371/journal.pone.0022150Lu Y.J., Yao J., Wei Q.J., Xing G.Q., Cao X. Diagnostic value of SLC26A4 mutation status in hereditary hearing loss with EVA: a PRISMA­compliant meta­analysis. Medicine (Baltimore). 2015; 94(50):e2248. doi: 10.1097/MD.0000000000002248Lu Y.J., Yao J., Wei Q.J., Xing G.Q., Cao X. Diagnostic value of SLC26A4 mutation status in hereditary hearing loss with EVA: a PRISMA­compliant meta­analysis. Medicine (Baltimore). 2015; 94(50):e2248. doi: 10.1097/MD.0000000000002248Mannai­ool M.Kh. Tuvan People. The Origin and Formation of the Ethnos. Novosibirsk: Nauka Publ., 2004 (in Russian)Mannai­ool M.Kh. Tuvan People. The Origin and Formation of the Ethnos. Novosibirsk: Nauka Publ., 2004 (in Russian)Mongush M.V. Tuvans of Mongolia and China. Int J Cent Asian Stud. 1996;1:225-243Mongush M.V. Tuvans of Mongolia and China. Int J Cent Asian Stud. 1996;1:225-243Nance W.E., Kearsey M.J. Relevance of connexin deafness (DFNB1) to human evolution. Am J Hum Genet. 2004;74(6):1081­1087. doi: 10.1086/420979Nance W.E., Kearsey M.J. Relevance of connexin deafness (DFNB1) to human evolution. Am J Hum Genet. 2004;74(6):1081­1087. doi: 10.1086/420979Nance W.E., Liu X.Z., Pandya A. Relation between choice of partner and high frequency of connexin-26 deafness. Lancet. 2000; 356(9228):500­501. doi: 10.1016/S0140­6736(00)02565­4Nance W.E., Liu X.Z., Pandya A. Relation between choice of partner and high frequency of connexin-26 deafness. Lancet. 2000; 356(9228):500­501. doi: 10.1016/S0140­6736(00)02565­4Park H.J., Shaukat S., Liu X.Z., Hahn S.H., Naz S., Ghosh M., Kim H.N., Moon S.K., Abe S., Tukamoto K., Riazuddin S., Kabra M., Erdenetungalag R., Radnaabazar J., Khan S., Pandya A., Usami S.I., Nance W.E., Wilcox E.R., Riazuddin S., Griffith A.J. Origins and frequencies of SLC26A4 (PDS) mutations in east and south Asians: global implications for the epidemiology of deafness. J Med Genet. 2003;40(4):242­248. doi: 10.1136/jmg.40.4.242Park H.J., Shaukat S., Liu X.Z., Hahn S.H., Naz S., Ghosh M., Kim H.N., Moon S.K., Abe S., Tukamoto K., Riazuddin S., Kabra M., Erdenetungalag R., Radnaabazar J., Khan S., Pandya A., Usami S.I., Nance W.E., Wilcox E.R., Riazuddin S., Griffith A.J. Origins and frequencies of SLC26A4 (PDS) mutations in east and south Asians: global implications for the epidemiology of deafness. J Med Genet. 2003;40(4):242­248. doi: 10.1136/jmg.40.4.242Razdan S., Raina S.K., Pandita K.K., Razdan S., Nanda R., Kaul R., Dogra S. Inbreeding as a cause for deafness: Dadhkai study. Indian J Hum Genet. 2012;18(1):71­74. doi: 10.4103/0971­6866.96655Razdan S., Raina S.K., Pandita K.K., Razdan S., Nanda R., Kaul R., Dogra S. Inbreeding as a cause for deafness: Dadhkai study. Indian J Hum Genet. 2012;18(1):71­74. doi: 10.4103/0971­6866.96655Risch N., de Leon D., Ozelius L., Kramer P., Almasy L., Singer B., Fahn S., Breakefield X., Bressman S. Genetic analysis of idiopathic torsion dystonia in Ashkenazi Jews and their recent descent from a small founder population. Nat Genet. 1995;9(2):152-159. doi: 10.1038/ng0295­152Risch N., de Leon D., Ozelius L., Kramer P., Almasy L., Singer B., Fahn S., Breakefield X., Bressman S. Genetic analysis of idiopathic torsion dystonia in Ashkenazi Jews and their recent descent from a small founder population. Nat Genet. 1995;9(2):152-159. doi: 10.1038/ng0295­152Scott D.A., Carmi R., Elbedour K., Duyk G.M., Stone E.M., Sheffield V.C. Nonsyndromic autosomal recessive deafness is linked to the DFNB1 locus in a large inbred Bedouin family from Israel. Am J Hum Genet. 1995;57(4):965­698.Scott D.A., Carmi R., Elbedour K., Duyk G.M., Stone E.M., Sheffield V.C. Nonsyndromic autosomal recessive deafness is linked to the DFNB1 locus in a large inbred Bedouin family from Israel. Am J Hum Genet. 1995;57(4):965­698.Slatkin M., Rannala B. Estimating allele age. Annu Rev Genomics Hum Genet. 2000;1:225-249. doi: 10.1146/annurev.genom.1.1.225Slatkin M., Rannala B. Estimating allele age. Annu Rev Genomics Hum Genet. 2000;1:225-249. doi: 10.1146/annurev.genom.1.1.225Tsukada K., Nishio S.Y., Hattori M., Usami S. Ethnic­specific spectrum of GJB2 and SLC26A4 mutations : their origin and a literature review. Ann Otol Rhinol Laryngol. 2015;124(1):61S-76S. doi: 10.1177/0003489415575060Tsukada K., Nishio S.Y., Hattori M., Usami S. Ethnic­specific spectrum of GJB2 and SLC26A4 mutations : their origin and a literature review. Ann Otol Rhinol Laryngol. 2015;124(1):61S-76S. doi: 10.1177/0003489415575060Vainshtein S.I., Mannay­Ool M.H. (Eds) History of Tyva. Vol. 1. Novosibirsk: Nauka Publ., 2001 (in Russian)Vainshtein S.I., Mannay­Ool M.H. (Eds) History of Tyva. Vol. 1. Novosibirsk: Nauka Publ., 2001 (in Russian)Wasano K., Takahashi S., Rosenberg S.K., Kojima T., Mutai H., Matsunaga T., Ogawa K., Homma K. Systematic quantification of the anion transport function of pendrin (SLC26A4) and its disease-associated variants. Hum Mutat. 2020;41(1):316-331. doi: 10.1002/humu.23930Wasano K., Takahashi S., Rosenberg S.K., Kojima T., Mutai H., Matsunaga T., Ogawa K., Homma K. Systematic quantification of the anion transport function of pendrin (SLC26A4) and its disease-associated variants. Hum Mutat. 2020;41(1):316-331. doi: 10.1002/humu.23930Wu C.C., Yeh T.H., Chen P.J., Hsu C.J. Prevalent SLC26A4 mutations in patients with enlarged vestibular aqueduct and/or Mondini dysplasia: a unique spectrum of mutations in Taiwan, including a frequent founder mutation. Laryngoscope. 2005;115(6):1060-1064. doi: 10.1097/01.MLG.0000163339.61909.D0Wu C.C., Yeh T.H., Chen P.J., Hsu C.J. Prevalent SLC26A4 mutations in patients with enlarged vestibular aqueduct and/or Mondini dysplasia: a unique spectrum of mutations in Taiwan, including a frequent founder mutation. Laryngoscope. 2005;115(6):1060-1064. doi: 10.1097/01.MLG.0000163339.61909.D0Yang J.J., Tsai C.C., Hsu H.M., Shiao J.Y., Su C.C., Li S.Y. Hearing loss associated with enlarged vestibular aqueduct and Mondini dysplasia is caused by splice-site mutation in the PDS gene. Hear Res. 2005;199(1­2):22­30. doi: 10.1016/j.heares.2004.08.007Yang J.J., Tsai C.C., Hsu H.M., Shiao J.Y., Su C.C., Li S.Y. Hearing loss associated with enlarged vestibular aqueduct and Mondini dysplasia is caused by splice-site mutation in the PDS gene. Hear Res. 2005;199(1­2):22­30. doi: 10.1016/j.heares.2004.08.007Yang X.L., Bai­-Cheng X., Chen X.J., Pan­Pan B., Jian­Li M., Xiao-Wen L., Zhang Z.W., Wan D., Zhu Y.M., Guo Y.F. Common molecular etiology of patients with nonsyndromic hearing loss in Tibetan, Tu nationality, and Mongolian patients in the northwest of China. Acta Otolaryngol. 2013;133(9):930­934. doi: 10.3109/00016489.2013.795288Yang X.L., Bai­-Cheng X., Chen X.J., Pan­Pan B., Jian­Li M., Xiao-Wen L., Zhang Z.W., Wan D., Zhu Y.M., Guo Y.F. Common molecular etiology of patients with nonsyndromic hearing loss in Tibetan, Tu nationality, and Mongolian patients in the northwest of China. Acta Otolaryngol. 2013;133(9):930­934. doi: 10.3109/00016489.2013.795288Yoon J.S., Park H.J., Yoo S.Y., Namkung W., Jo M.J., Koo S.K., Park H.Y., Lee W.S., Kim K.H., Lee M.G. Heterogeneity in the processing defect of SLC26A4 mutants. J Med Genet. 2008;45(7):411-419. doi: 10.1136/jmg.2007.054635Yoon J.S., Park H.J., Yoo S.Y., Namkung W., Jo M.J., Koo S.K., Park H.Y., Lee W.S., Kim K.H., Lee M.G. Heterogeneity in the processing defect of SLC26A4 mutants. J Med Genet. 2008;45(7):411-419. doi: 10.1136/jmg.2007.054635Zlotogora J. Multiple mutations responsible for frequent genetic diseases in isolated populations. Eur J Hum Genet. 2007;15(3):272-278. doi: 10.1038/sj.ejhg.5201760Zlotogora J. Multiple mutations responsible for frequent genetic diseases in isolated populations. Eur J Hum Genet. 2007;15(3):272-278. doi: 10.1038/sj.ejhg.5201760

The authors declare that there are no conflicts of interest present.