ymjЯкутский медицинский журналYakut Medical Journal1813-19052312-1017ЯНЦ КМП10.25789/YMJ.2025.90.06ymj-768Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL RESEARCHАтипичные случаи снижения слуха у пациентов с митохондриальным вариантом m.1555A>G гена MT-RNR1 в БурятииAtypical cases of hearing loss in patients with the mitochondrial variant m.1555A>G of the MT-RNR1 gene in the Republic of Buryatiahttps://orcid.org/0000-0002-8659-0886ТерютинФ. М.TeryutinF. M.

Терютин Федор Михайлович – к.м.н., н.с.

677000, Якутск, ул. Ярославского, 6/3

rest26@mail.ruhttps://orcid.org/0000-0002-5019-067XБорисоваТ. В.BorisovaT. V.

БОРИСОВА Туяра Валерьевна – м.н.с. ИЕН, 

 

psennikovavera@mail.ruhttps://orcid.org/0000-0002-4168-9516ЧердоноваА. М.CherdonovaA. M.

Чердонова Александра Матвеевна – м.н.с. ИЕН.

677000, Якутск, ул. Кулаковского, 48

cherdonovasasha96@gmail.comhttps://orcid.org/0000-0002-2936-5818РомановГ. П.RomanovG. P.

Романов Георгий Прокопьевич – к.б.н., н.с. ИЕН.

677000, Якутск, ул. Кулаковского, 48

gpromanov@gmail.comhttps://orcid.org/0000-0001-6866-9462ПшенниковаВ. Г.PshennikovaV. G.

Пшенникова Вера Геннадиевна – к.б.н., в.н.с., руковод. лаб.

677000, Якутск, ул. Ярославского, 6/3

psennikovavera@mail.ruhttps://orcid.org/0000-0003-0914-3609СоловьевА. В.SolovyovA. V.

Соловьев Айсен Васильевич – к.б.н., с.н.с. ИЕН.

677000, Якутск, ул. Кулаковского, 48

nelloann@mail.ruhttps://orcid.org/0000-0002-6952-3868ФедороваС. А.FedorovaS. A.

Федорова Сардана Аркадьевна – д.б.н., зав. лаб. ИЕН, с.н.с. ЯНЦ КМП.

677000, Якутск, ул. Кулаковского, 48

sardaanafedorova@mail.ruhttps://orcid.org/0000-0002-6984-7934БарашковН. А.BarashkovN. A.

Барашков Николай Алексеевич – к.б.н., в.н.с.руковод. лаб.

677000, Якутск, ул. Ярославского, 6/3

barashkov2004@mail.ruЯкутский научный центр комплексных медицинских проблемРоссияСеверо-Восточный федеральный университет им. М.К. АммосоваРоссия202522062025022933Copyright © Терютин Ф.М., Борисова Т.В., Чердонова А.М., Романов Г.П., Пшенникова В.Г., Соловьев А.В., Федорова С.А., Барашков Н.А., 20252025Терютин Ф.М., Борисова Т.В., Чердонова А.М., Романов Г.П., Пшенникова В.Г., Соловьев А.В., Федорова С.А., Барашков Н.А.Teryutin F.M., Borisova T.V., Cherdonova A.M., Romanov G.P., Pshennikova V.G., Solovyov A.V., Fedorova S.A., Barashkov N.A.This work is licensed under a Creative Commons Attribution 4.0 License.https://ymj.elpub.ru/jour/article/view/768

В ранее проведенном исследовании мы обнаружили высокую распространенность варианта m.1555A>G гена MT-RNR1, приводящего к митохондриальной форме потери слуха (MT-RNR1, OMIM 561000), среди пациентов с тугоухостью и глухотой, проживающих в регионе озера Байкал. В связи с этим в настоящей работе в обнаруженном сибирском очаге накопления данного митохондриального заболевания проведен генотип-фенотипический анализ слуховой функции у индивидов с вариантом m.1555A>G. Клинико-аудиологический анализ был проведен у 48 чел. с m.1555A>G, средний возраст которых составил 51,3±15,5 года. Полученные генотип-фенотипические характеристики согласуются с ранее проведенными исследованиями особенностей слуховой функции у индивидов с m.1555A>G, которые отмечают неполную пенетрантность проявления патологического фенотипа в пораженных семьях. В исследованной когорте особый интерес представляют три случая смешанного типа снижения слуха, включающего как сенсоневральный (патология внутреннего уха), так и кондуктивный компонент (патология среднего уха), который не характерен для митохондриальной формы потери слуха (MT-RNR1). Авторами не исключается вероятность того, что обнаруженные клинические признаки могут быть следствием ранее не описанного системного поражения органа слуха при митохондриальном варианте m.1555A>G гена MT-RNR1. Вместе с тем обнаруженные случаи могут быть связаны с перекрестным патологическим эффектом, обусловленным другой формой менее распространенного или редкого заболевания, что требует дальнейших молекулярно-генетических исследований.

In the previous study, we found a high prevalence of the m.1555A>G variant of the MT-RNR1 gene, which causes mitochondrial hearing loss (OMIM 561000) among deaf patients living in the Baikal Lake region. In this regard, in the present study, a genotype-phenotypic analysis of the hearing function in individuals with the m.1555A>G variant was carried out in the discovered Siberian region. Clinical and audiological analysis was performed in 48 people with this mitochondrial variant, whose average age was 51.3±15.5 years. The obtained genotype-phenotypic data are consistent with previously conducted studies of the features of the auditory function in individuals with m.1555A>G, which note incomplete penetrance of the manifestation of the pathological phenotype. Of particular interest in our cohort are three cases of mixed hearing loss, including both sensorineural (inner ear defect) and conductive (middle ear defect) components. We do not exclude the possibility that the detected clinical signs may be a consequence of systemic damage to the hearing organ in this mitochondrial variant. On the other hand, the detected cases may be associated with a cross-pathological effect caused by another form of a less common or rare disease, which requires further molecular genetic studies.

митохондриальная потеря слухавариант m.1555A>Gген MT-RNR1генотип-фенотипический анализБурятияmitochondrial hearing lossm.1555A>G variantMT-RNR1 genegenotype-phenotypic analysisBuryatiaРабота выполнена в рамках НИР ЯНЦ КМП «Изучение генетической структуры и груза наследственной патологии в популяциях Республики Саха (Якутия)» и Государственного задания Министерства науки и высшего образования РФ (FSRG-20230003)ReferencesA new locus for otosclerosis, OTSC8, maps to the pericentromeric region of chromosome 9 / I. Bel Hadj Ali, M. Thys, N. Beltaief [et al.] // Hum Genet. 2008. 123:267–272. https://doi.org/10.1007/s00439-008-0470-3A new locus for otosclerosis, OTSC8, maps to the pericentromeric region of chromosome 9 / I. Bel Hadj Ali, M. Thys, N. Beltaief [et al.] // Hum Genet. 2008. 123:267–272. https://doi.org/10.1007/s00439-008-0470-3A new locus for otosclerosis, OTSC10, maps to chromosome 1q41-44 / I. Schrauwen, N.J. Weegerink, E. Fransen [et al.] // Clin Genet. 2011. 79:495–497. https://doi.org/10.1111/j.1399-0004.2010.01576.xA new locus for otosclerosis, OTSC10, maps to chromosome 1q41-44 / I. Schrauwen, N.J. Weegerink, E. Fransen [et al.] // Clin Genet. 2011. 79:495–497. https://doi.org/10.1111/j.1399-0004.2010.01576.xA pathogenic deletion in Forkhead Box L1 (FOXL1) identifies the first otosclerosis (OTSC) gene / N. Abdelfatah, A.A. Mostafa, C.R. French [et al.] // Hum Genet. 2022. 141(3-4):965-979. doi: 10.1007/s00439-021-02381-1.A pathogenic deletion in Forkhead Box L1 (FOXL1) identifies the first otosclerosis (OTSC) gene / N. Abdelfatah, A.A. Mostafa, C.R. French [et al.] // Hum Genet. 2022. 141(3-4):965-979. doi: 10.1007/s00439-021-02381-1.A second gene for otosclerosis, OTSC2, maps to chromosome 7q34-36 / K. Van Den Bogaert, P.J. Govaerts, I. Schatteman [et al.] // Am J Hum Genet. 2001. 68:495–500. https://doi.org/10.1086/318185A second gene for otosclerosis, OTSC2, maps to chromosome 7q34-36 / K. Van Den Bogaert, P.J. Govaerts, I. Schatteman [et al.] // Am J Hum Genet. 2001. 68:495–500. https://doi.org/10.1086/318185Babcock T.A., Liu X.Z. Otosclerosis: From Genetics to Molecular Biology // Otolaryngol Clin North Am. 2018. 51:305–318. https://doi.org/10.1016/j.otc.2017.11.002Babcock T.A., Liu X.Z. Otosclerosis: From Genetics to Molecular Biology // Otolaryngol Clin North Am. 2018. 51:305–318. https://doi.org/10.1016/j.otc.2017.11.002Bravo O., Ballana E., Estivill X. Cochlear Alterations in Deaf and Unaffected Subjects Carrying the Deaf-ness-Associated A1555G Mutation in the Mitochondrial 12S rRNA Gene // Biochem Biophys Res Commun. 2006. 344, 511–516, doi:10.1016/j.bbrc.2006.03.143.Bravo O., Ballana E., Estivill X. Cochlear Alterations in Deaf and Unaffected Subjects Carrying the Deaf-ness-Associated A1555G Mutation in the Mitochondrial 12S rRNA Gene // Biochem Biophys Res Commun. 2006. 344, 511–516, doi:10.1016/j.bbrc.2006.03.143.Candidate locus for a nuclear modifier gene for maternally inherited deafness / Y. Bykhovskaya, X. Estivill, K. Taylor [et al.] // American journal of human genetics. 2000. 66(6), 1905–1910. https://doi.org/10.1086/302914Candidate locus for a nuclear modifier gene for maternally inherited deafness / Y. Bykhovskaya, X. Estivill, K. Taylor [et al.] // American journal of human genetics. 2000. 66(6), 1905–1910. https://doi.org/10.1086/302914Chromosomal mapping and phenotypic characterization of hereditary otosclerosis linked to the OTSC4 locus / Z. Brownstein, A. Goldfarb, H. Levi [et al.] // Arch Otolaryngol Head Neck Surg. 2006. 132:416–424. https://doi.org/10.1001/archotol.132.4.416Chromosomal mapping and phenotypic characterization of hereditary otosclerosis linked to the OTSC4 locus / Z. Brownstein, A. Goldfarb, H. Levi [et al.] // Arch Otolaryngol Head Neck Surg. 2006. 132:416–424. https://doi.org/10.1001/archotol.132.4.416Deafness due to A1555G mitochondrial mutation without use of aminoglycoside / T. Matsunaga, H. Kumanomido, M. Shiroma [et al.] // Laryngoscope. 2004. 114. 1085-91. doi: 10.1097/00005537-200406000-00024.Deafness due to A1555G mitochondrial mutation without use of aminoglycoside / T. Matsunaga, H. Kumanomido, M. Shiroma [et al.] // Laryngoscope. 2004. 114. 1085-91. doi: 10.1097/00005537-200406000-00024.Familial Progressive Sensorineural Deafness Is Mainly Due to the MtDNA A1555G Mutation and Is Enhanced by Treatment of Aminoglycosides / X. Estivill, N. Govea, E. Barceló [et al.] // Am J Hum Genet. 1998. 62. 27–35. doi:10.1086/301676.Familial Progressive Sensorineural Deafness Is Mainly Due to the MtDNA A1555G Mutation and Is Enhanced by Treatment of Aminoglycosides / X. Estivill, N. Govea, E. Barceló [et al.] // Am J Hum Genet. 1998. 62. 27–35. doi:10.1086/301676.Finsterer J. Variant m.1555A>G in MT-RNR1 causes hearing loss and multiorgan mitochondrial disorder // Medicine (Baltimore). 2020 99(6):e18488. doi: 10.1097/MD.0000000000018488.Finsterer J. Variant m.1555A>G in MT-RNR1 causes hearing loss and multiorgan mitochondrial disorder // Medicine (Baltimore). 2020 99(6):e18488. doi: 10.1097/MD.0000000000018488.Guan M.X., Fischel-Ghodsian N., Attardi G. Biochemical Evidence for Nuclear Gene Involvement in Phenotype of Non-Syndromic Deafness Associated with Mitochondrial 12S RRNA Mutation // Hum Mol Genet. 1996. 5. 963–971. doi:10.1093/hmg/5.7.963.Guan M.X., Fischel-Ghodsian N., Attardi G. Biochemical Evidence for Nuclear Gene Involvement in Phenotype of Non-Syndromic Deafness Associated with Mitochondrial 12S RRNA Mutation // Hum Mol Genet. 1996. 5. 963–971. doi:10.1093/hmg/5.7.963.Hamasaki K., Rando R.R. Specific Binding of Aminoglycosides to a Human RRNA Construct Based on a DNA Polymorphism Which Causes Aminoglycoside-Induced Deafness // Biochemistry. 1997. 36. 12323–12328, doi:10.1021/bi970962r.Hamasaki K., Rando R.R. Specific Binding of Aminoglycosides to a Human RRNA Construct Based on a DNA Polymorphism Which Causes Aminoglycoside-Induced Deafness // Biochemistry. 1997. 36. 12323–12328, doi:10.1021/bi970962r.Heterozygous SSBP1 start loss mutation co-segregates with hearing loss and the m.1555A>G mtDNA variant in a large multigenerational family / P.J. Kullar, A. Gomez-Duran, P.A. Gammage [et al.] // Brain. 2018. 141(1):55-62. doi: 10.1093/brain/awx295.Heterozygous SSBP1 start loss mutation co-segregates with hearing loss and the m.1555A>G mtDNA variant in a large multigenerational family / P.J. Kullar, A. Gomez-Duran, P.A. Gammage [et al.] // Brain. 2018. 141(1):55-62. doi: 10.1093/brain/awx295.High prevalence of m.1555A> G in patients with hearing loss in the Baikal Lake region of Russia as a result of founder effect / T.V. Borisova, A.M. Cherdonova, V.G. Pshennikova [et al.] // Sci Rep. 2024. 14(1):15342. doi: 10.1038/s41598-024-66254-z.High prevalence of m.1555A> G in patients with hearing loss in the Baikal Lake region of Russia as a result of founder effect / T.V. Borisova, A.M. Cherdonova, V.G. Pshennikova [et al.] // Sci Rep. 2024. 14(1):15342. doi: 10.1038/s41598-024-66254-z.In Silico Model of mtDNA Mutations Effect on Secondary and 3D Structure of Mitochondrial rRNA and tRNA in Leber’s Hereditary Optic Neuropathy / B. Rovcanin, J. Jancic, J. Samardzic [et al.] // Exp Eye Res. 2020. 201. 108277, doi:10.1016/j.exer.2020.108277.In Silico Model of mtDNA Mutations Effect on Secondary and 3D Structure of Mitochondrial rRNA and tRNA in Leber’s Hereditary Optic Neuropathy / B. Rovcanin, J. Jancic, J. Samardzic [et al.] // Exp Eye Res. 2020. 201. 108277, doi:10.1016/j.exer.2020.108277.Linkage of otosclerosis to a third locus (OTSC3) on human chromosome 6p21.3-22.3 / W. Chen, C.A. Campbell, G.E. Green [et al.] //j Med Genet. 2002. 39:473–477. https://doi.org/10.1136/jmg.39.7.473Linkage of otosclerosis to a third locus (OTSC3) on human chromosome 6p21.3-22.3 / W. Chen, C.A. Campbell, G.E. Green [et al.] //j Med Genet. 2002. 39:473–477. https://doi.org/10.1136/jmg.39.7.473Li X., Guan M.X. A human mitochondrial GTP binding protein related to tRNA modification may modulate phenotypic expression of the deafness-associated mitochondrial 12S rRNA mutation // Mol Cell Biol. 2002. 22(21):7701-11. doi: 10.1128/MCB.22.21.7701-7711.2002.Li X., Guan M.X. A human mitochondrial GTP binding protein related to tRNA modification may modulate phenotypic expression of the deafness-associated mitochondrial 12S rRNA mutation // Mol Cell Biol. 2002. 22(21):7701-11. doi: 10.1128/MCB.22.21.7701-7711.2002.Localization of a gene for otosclerosis to chromosome 15q25-q26 / M.S. Tomek, M.R. Brown, S.R. Mani [et al.] // Hum Mol Genet. 1998. 7:285–290. https://doi.org/10.1093/hmg/7.2.285Localization of a gene for otosclerosis to chromosome 15q25-q26 / M.S. Tomek, M.R. Brown, S.R. Mani [et al.] // Hum Mol Genet. 1998. 7:285–290. https://doi.org/10.1093/hmg/7.2.285Mitchell P. Coupling of phosphorylation to electron and hydrogen transfer by a chemi-osmotic type of mechanism // Nature. 1961 Jul 8;191:144-8. doi: 10.1038/191144a0.Mitchell P. Coupling of phosphorylation to electron and hydrogen transfer by a chemi-osmotic type of mechanism // Nature. 1961 Jul 8;191:144-8. doi: 10.1038/191144a0.Mitochondrial Gene Mutation Is a Significant Predisposing Factor in Aminoglycoside Ototoxicity / N. Fischel-Ghodsian, T.R. Prezant, W.E. Chaltraw [et al.] // Am J Otolaryngol. 1997. 18. 173–178. doi:10.1016/s0196-0709(97)90078-8.Mitochondrial Gene Mutation Is a Significant Predisposing Factor in Aminoglycoside Ototoxicity / N. Fischel-Ghodsian, T.R. Prezant, W.E. Chaltraw [et al.] // Am J Otolaryngol. 1997. 18. 173–178. doi:10.1016/s0196-0709(97)90078-8.Mitochondrial Ribosomal RNA Gene Mutation in a Patient with Sporadic Aminoglycoside Ototoxicity // N. Fischel-Ghodsian, T.R. Prezant, X. Bu [et al.] // Am J Otolaryngol. 1993. 14. 399– 403, doi:10.1016/0196-0709(93)90113-l.Mitochondrial Ribosomal RNA Gene Mutation in a Patient with Sporadic Aminoglycoside Ototoxicity // N. Fischel-Ghodsian, T.R. Prezant, X. Bu [et al.] // Am J Otolaryngol. 1993. 14. 399– 403, doi:10.1016/0196-0709(93)90113-l.Mitochondrial Deafness Alleles Confer Misreading of the Genetic Code / S.N. Hobbie, C.M. Bruell, S. Akshay [et al.] // Proc Natl Acad Sci USA. 2008. 105. 3244–3249. doi:10.1073/pnas.0707265105.Mitochondrial Deafness Alleles Confer Misreading of the Genetic Code / S.N. Hobbie, C.M. Bruell, S. Akshay [et al.] // Proc Natl Acad Sci USA. 2008. 105. 3244–3249. doi:10.1073/pnas.0707265105.Mitochondrial Ribosomal RNA Mutation Associated with Both Antibiotic-Induced and Non-Syndromic Deafness / T.R. Prezant, J.V. Agapian, M.C. Bohlman [et al.] // Nat Genet. 1993. 4. 289–294. doi:10.1038/ng0793-289.Mitochondrial Ribosomal RNA Mutation Associated with Both Antibiotic-Induced and Non-Syndromic Deafness / T.R. Prezant, J.V. Agapian, M.C. Bohlman [et al.] // Nat Genet. 1993. 4. 289–294. doi:10.1038/ng0793-289.Molecular Basis for Human Hypersensitivity to Aminoglycoside Antibiotics / T. Hutchin, I. Haworth, K. Higashi [et al.] //Nucleic Acids Res. 1993. 21, 4174–4179, doi:10.1093/nar/21.18.4174Molecular Basis for Human Hypersensitivity to Aminoglycoside Antibiotics / T. Hutchin, I. Haworth, K. Higashi [et al.] //Nucleic Acids Res. 1993. 21, 4174–4179, doi:10.1093/nar/21.18.4174Mutation of foxl1 Results in Reduced Cartilage Markers in a Zebrafish Model of Otosclerosis / A. Hawkey-Noble, J.A. Pater, R. Kollipara [et al.] // Genes (Basel). 2022. 13(7):1107. doi: 10.3390/genes13071107.Mutation of foxl1 Results in Reduced Cartilage Markers in a Zebrafish Model of Otosclerosis / A. Hawkey-Noble, J.A. Pater, R. Kollipara [et al.] // Genes (Basel). 2022. 13(7):1107. doi: 10.3390/genes13071107.Mutation in TRMU related to transfer RNA modification modulates the phenotypic expression of the deafness-associated mitochondrial 12S ribosomal RNA mutations / M.X. Guan, Q. Yan, X. Li, Y. Bykhovskaya [et al.] // American journal of human genetics. 2006. 79(2), 291–302. https://doi.org/10.1086/506389Mutation in TRMU related to transfer RNA modification modulates the phenotypic expression of the deafness-associated mitochondrial 12S ribosomal RNA mutations / M.X. Guan, Q. Yan, X. Li, Y. Bykhovskaya [et al.] // American journal of human genetics. 2006. 79(2), 291–302. https://doi.org/10.1086/506389Otosclerosis: etiopathogenesis and histopathology / S. Cureoglu, P.A. Schachern, A. Ferlito [et al.] // Am J Otolaryngol. 2006. 27:334–340. https://doi.org/10.1016/j.amjoto.2005.11.001Otosclerosis: etiopathogenesis and histopathology / S. Cureoglu, P.A. Schachern, A. Ferlito [et al.] // Am J Otolaryngol. 2006. 27:334–340. https://doi.org/10.1016/j.amjoto.2005.11.001Primer-BLAST: A Tool to Design Target-Specific Primers for Polymerase Chain Reaction /j. Ye, G. Coulouris G, I. Zaretskaya [et al.] // BMC Bioinformatics. 2012. 13, 134, doi:10.1186/1471-2105-13-134.Primer-BLAST: A Tool to Design Target-Specific Primers for Polymerase Chain Reaction /j. Ye, G. Coulouris G, I. Zaretskaya [et al.] // BMC Bioinformatics. 2012. 13, 134, doi:10.1186/1471-2105-13-134.Ribosome. The Complete Structure of the 55S Mammalian Mitochondrial Ribosome / B.J. Greber, P. Bieri, M. Leibundgut [et al.] // Science. 2015. 348, 303–308, doi:10.1126/science.aaa3872.Ribosome. The Complete Structure of the 55S Mammalian Mitochondrial Ribosome / B.J. Greber, P. Bieri, M. Leibundgut [et al.] // Science. 2015. 348, 303–308, doi:10.1126/science.aaa3872.Rich P.R, Maréchal A. The mitochondrial respiratory chain // Essays Biochem. 2010. 47:1-23. doi: 10.1042/bse0470001.Rich P.R, Maréchal A. The mitochondrial respiratory chain // Essays Biochem. 2010. 47:1-23. doi: 10.1042/bse0470001.Sensorineural Hearing Loss in Patients With the m.1555A>G Mutation in the MTRNR1 Gene /j. Gallo-Terán, C. Salomón-Felechosa, R. González-Aguado [et al.] // Laryngoscope. 2024. doi: 10.1002/lary.31796.Sensorineural Hearing Loss in Patients With the m.1555A>G Mutation in the MTRNR1 Gene /j. Gallo-Terán, C. Salomón-Felechosa, R. González-Aguado [et al.] // Laryngoscope. 2024. doi: 10.1002/lary.31796.Septo-optic dysplasia associated with a new mitochondrial cytochrome b mutation / M. Schuelke, H. Krude, B. Finckh [et al.] // Ann. Neurol. 2002. 51: 388-392.Septo-optic dysplasia associated with a new mitochondrial cytochrome b mutation / M. Schuelke, H. Krude, B. Finckh [et al.] // Ann. Neurol. 2002. 51: 388-392.The Genetic Landscape of Mitochondrial Diseases in Spain: A Nationwide Call / M. Bellusci, A.J. Paredes-Fuentes, E. Ruiz-Pesini [et al.] // Genes (Basel). 2021. 12. 1590. doi:10.3390/genes12101590.The Genetic Landscape of Mitochondrial Diseases in Spain: A Nationwide Call / M. Bellusci, A.J. Paredes-Fuentes, E. Ruiz-Pesini [et al.] // Genes (Basel). 2021. 12. 1590. doi:10.3390/genes12101590.Thys M., Van Camp G. Genetics of otosclerosis // Otol Neurotol. 2009. 30:1021–1032. https://doi.org/10.1097/MAO.0b013e3181a86509Thys M., Van Camp G. Genetics of otosclerosis // Otol Neurotol. 2009. 30:1021–1032. https://doi.org/10.1097/MAO.0b013e3181a86509Thys M., Van Den Bogaert K., Iliadou V. A seventh locus for otosclerosis, OTSC7, maps to chromosome 6q13-16.1 // Eur J Hum Genet. 2007. 15:362–368. https://doi.org/10.1038/sj.ejhg.5201761Thys M., Van Den Bogaert K., Iliadou V. A seventh locus for otosclerosis, OTSC7, maps to chromosome 6q13-16.1 // Eur J Hum Genet. 2007. 15:362–368. https://doi.org/10.1038/sj.ejhg.5201761Van Den Bogaert K., De Leenheer E.M., Chen W. A fifth locus for otosclerosis, OTSC5, maps to chromosome 3q22-24 //j Med Genet. 2004. 41:450–453. https://doi.org/10.1136/jmg.2004.018671Van Den Bogaert K., De Leenheer E.M., Chen W. A fifth locus for otosclerosis, OTSC5, maps to chromosome 3q22-24 //j Med Genet. 2004. 41:450–453. https://doi.org/10.1136/jmg.2004.018671

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