ymjЯкутский медицинский журналYakut Medical Journal1813-19052312-1017ЯНЦ КМП10.25789/YMJ.2024.85.07ymj-343Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL RESEARCHРедкий вариант с.7636C>T p.(Gln2546*) гена MYO15A у двоих пациентов из Бурятии с сенсоневральной глухотойA rare variant of p.7636C>T p.(Gln2546*) of the MYO15A gene in two patients from Buryatia with sensorineural deafnesshttps://orcid.org/0000-0002-4168-9516ЧердоноваА. М.CherdonovaA. M.

ЧЕРДОНОВА Александра Матвеевна – аспирант

CHERDONOVA Aleksandra Matveevna – postgraduate student

https://orcid.org/0000-0002-5019-067XБорисоваТ. В.BorisovaT. V.

БОРИСОВА Туяра Валерьевна – аспирант

BORISOVA Tuyara Valeryevna – postgraduate student

https://orcid.org/0000-0002-8659-0886ТерютинФ. М.TeryutinF. M.

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

TERYUTIN Fyodor Mikhailovich – PhD

https://orcid.org/0000-0001-6866-9462ПшенниковаВ. Г.PshennikovaV. G.

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

PSHENNIKOVA Vera Gennadievna – PhD in Biology

https://orcid.org/0000-0003-0914-3609СоловьевА. В.SolovievA. V.

СОЛОВЬЕВ Айсен Васильевич – к.б.н., с.н.с.

SOLOVIEV Aisen Vasilyevich – PhD in Biology

https://orcid.org/0000-0002-2936-5818РомановГ. П.RomanovG. P.

РОМАНОВ Георгий Прокопьевич – к.б.н., н.с.

ROMANOV Georgy Prokopievich - PhD in Biology

https://orcid.org/0000-0002-6952-3868ФедороваС. А.FedorovaS. A.

ФЕДОРОВА Сардана Аркадьевна – д.б.н., гл.н.с.

FEDOROVA Sardana Arkadyevna – Doctor in Biology

https://orcid.org/0000-0002-6984-7934БарашковН. А.BarashkovN. A.

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

BARASHKOV Nikolay Alekseevich – PhD in Biology

Северо-Восточный федеральный университет им. М.К. АммосоваРоссияM.K. Ammosov North-Eastern Federal UniversityRussian FederationЯкутский научный центр комплексных медицинских проблемРоссияYakut Scientific Centre of Complex Medical ProblemsRussian Federation202409022025012729Copyright © Чердонова А.М., Борисова Т.В., Терютин Ф.М., Пшенникова В.Г., Соловьев А.В., Романов Г.П., Федорова С.А., Барашков Н.А., 20252025Чердонова А.М., Борисова Т.В., Терютин Ф.М., Пшенникова В.Г., Соловьев А.В., Романов Г.П., Федорова С.А., Барашков Н.А.Cherdonova A.M., Borisova T.V., Teryutin F.M., Pshennikova V.G., Soloviev A.V., Romanov G.P., Fedorova S.A., Barashkov N.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://ymj.elpub.ru/jour/article/view/343

Роль патогенных вариантов гена MYO15A в этиологии потери слуха в мире слабо изучена, поскольку относительно крупный размер гена (66 экзонов) предполагает поиск каузативных вариантов с использованием NGS технологий, которые пока в недостаточной степени используются в рутинной практике. Целью данной работы является описание редкого варианта c.7636C>T p.(Gln2546*) гена MYO15A, обнаруженного в гомозиготном состоянии у двоих сибсов с прелингвальной глубокой сенсоневральной потерей слуха из бурятской семьи. Ранее этот вариант был найден только у одного пациента в компаунд-гетерозиготном состоянии с другим нонсенс-вариантом гена MYO15A в Бразилии и описан как патогенный. Идентификация варианта c.7636C>T p.(Gln2546*) в гомозиготном состоянии у бурятских сибсов может свидетельствовать либо о редком случае эндогамного брака, либо о более широком распространении данного варианта в регионе озера Байкал.

In the world the role of pathogenic variants of the MYO15A gene in the etiology of hearing loss has not been sufficiently studied, since the large size of the gene (66 exons, 71 kb) suggests the search for pathogenic variants using NGS technologies, which are not yet sufficiently used in routine practice. In this regard, it is relevant to study the role of pathogenic variants of the MYO15A gene in the etiology of non-syndromic forms of hearing impairments. The purpose of this work is to describe the rare pathogenic variant c.7636C>T p.(Gln2546*) in the MYO15A gene, found in a homozygous state in two siblings with prelingual profound sensorineural hearing loss from a Buryat family. Previously, this variant was found only in one patient in a compound-heterozygous state with another nonsense variant in the MYO15A gene in Brazil and described as pathogenic. Detection of variant c.7636C>T p.(Gln2546*) in a homozygous state in Buryat siblings may indicate either a rare case of endogamous marriage or a wider distribution of this variant in the Lake Baikal region.

аутосомно-рецессивная глухота (DFNB3)ген MYO15Aвариант c.7636C>T p.(Gln2546*)Республика Бурятияautosomal recessive deafness (DFNB3)MYO15A genevariant c.7636C>T p.(Gln2546*)Republic of BuryatiaРабота 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-2023- 0003).The work was carried out within the framework of the research of the YSC CMP "Study of the genetic structure and burden of hereditary pathology in the populations of the Republic of Sakha (Ya- kutia)» and the State assignment of the Ministry of Science and Higher Education of the Russian Federation (FSRG-2023- 0003).ReferencesРоссийский и международный опыт реализации программ универсального аудиологического скрининга новорожденных / Г.А. Таварткиладзе, Т.Г. Маркова, С.С. Чибисова [и др.] // Вестник оториноларингологии. 2016. №81(2). C.7-12.Tavartkiladze G.A., Markova T.G., Chibisova S.S. [et al.]. Rossiyskiy i mezhdunarodnyy opyt realizatsii programm universalnogo audiologicheskogo skrininga novorozhdennykh [The Russian and international experience with the implementation of the programs of universal audiological screening of the newborn infants]. Vestnik otorinolaringologii [Bulletin of otolaryngology. 2016; 81(2): 7-12 (In Russ.).] https://doi.org/10.17116/otorino20168127-12The Russian and international experience with the implementation of the programs of universal audiological screening of the newborn infants / G.A. Tavartkiladze, T.G. Markova, S.S. Chibisova [et al.] // Vestnik Oto-Rino-Laringologii. 2016. №81(2). P.7-12. https://doi.org/10.17116/otorino20168127-12Belyantseva, I.A., Boger, E.T., Friedman, T.B. Myosin XVa localizes to the tips of inner ear sensory cell stereocilia and is essential for staircase formation of the hair bundle. Proc Natl Acad Sci U S A. 2003; 100(24): 13958-63. doi: 10.1073/ pnas.2334417100.Belyantseva, I.A., Boger, E.T., Friedman, T.B. Myosin XVa localizes to the tips of inner ear sensory cell stereocilia and is essential for staircase formation of the hair bundle / I.A. Belyantseva, E.T. Boger, T.B. Friedman // Proc Natl Acad Sci U S A. – 2003. №100(24). – P.13958-63. doi: 10.1073/pnas.2334417100.Friedman T.B., Liang Y., Weber J.L. [et al.]. A gene for congenital, recessive deafness DFNB3 maps to the pericentromeric region of chromosome 17. Nat Genet. 1995; 9(1): 86-91. doi: 10.1038/ng0195-86.A gene for congenital, recessive deafness DFNB3 maps to the pericentromeric region of chromosome 17 / T.B. Friedman, Y. Liang, J.L. Weber [et al.] // Nat Genet. – 1995. №9(1). – P.86-91. doi: 10.1038/ng0195-86.Palombo F., Al-Wardy N., Ruscone G.A. [et al.]. A novel founder MYO15A frameshift duplication is the major cause of genetic hearing loss in Oman. J Hum Genet. 2017; 62(2): 259-264. doi: 10.1038/jhg.2016.120.A novel founder MYO15A frameshift duplication is the major cause of genetic hearing loss in Oman / F. Palombo, N. Al-Wardy, G.A. Ruscone [et al.] // J Hum Genet. – 2017. №62(2). P.259-264. doi: 10.1038/jhg.2016.120.Wang A, Liang Y., Fridell R.A. [et al.] Association of unconventional myosin MYO15 mutations with human nonsyndromic deafness DFNB3. Science. – 1998. – №280. – P.1447–1451. doi: 10.1126/science.280.5368.1447.Association of unconventional myosin MYO15 mutations with human nonsyndromic deafness DFNB3 / A. Wang, Y. Liang, R.A. Fridell [et al.] // Science. – 1998. – №280. – P.1447– 1451. doi: 10.1126/science.280.5368.1447.Castiglione A., Möller C. Usher Syndrome. Audiol Res. 2022; 12(1): 42-65. doi: 10.3390/audiolres12010005.Castiglione A., Möller C. Usher Syndrome. / A. Castiglione, C. Möller // Audiol Res. – 2022. №12(1). – P.42-65. doi: 10.3390/audiolres12010005.Chan D.K., Chang K.W. GJB2-associated hearing loss: systematic review of worldwide prevalence, genotype, and auditory phenotype. Laryngoscope. 2014; 124(2): E34-53. doi: 10.1002/lary.24332.Chan D.K., Chang K.W. GJB2-associated hearing loss: systematic review of worldwide prevalence, genotype, and auditory phenotype / D.K. Chan, K.W. Chang // Laryngoscope. – 2014. – №124(2). E34-53. doi: 10.1002/lary.24332.Liang Y., Liang, Wang A., Belyantseva I.A. [et al.]. Characterization of the human and mouse unconventional myosin XV genes responsible for hereditary deafness DFNB3 and shaker 2. Genomics. 1999; 61(3): 243-58. doi: 10.1006/geno.1999.5976.Characterization of the human and mouse unconventional myosin XV genes responsible for hereditary deafness DFNB3 and shaker 2 / Y. Liang, A. Wang, I.A. Belyantseva [et al.] // Genomics. – 1999. №61(3). – P.243-58. doi: 10.1006/geno.1999.5976.Del Castillo I., Morín M., Domínguez-Ruiz M. [et al.] Genetic etiology of non-syndromic hearing loss in Europe. Hum Genet. 2022; 141(3-4): 683-696. doi: 10.1007/s00439-02102425-6.Genetic etiology of non-syndromic hearing loss in Europe / I. Del Castillo, M. Morín, M. Domínguez-Ruiz [et al.] / Hum Genet. – 2022. №141(3-4) – P.683-696. doi: 10.1007/s00439021-02425-6.Zhang J, Guan J, Wang H [et al.]. Genotype-phenotype correlation analysis of MYO15A variants in autosomal recessive non-syndromic hearing loss. BMC Med Genet. 2019; 20(1): 60. doi: 10.1186/s12881-019-0790-2.Genotype-phenotype correlation analysis of MYO15A variants in autosomal recessive non-syndromic hearing loss / Zhang J, Guan J, Wang H [et al.] // BMC Med Genet. – 2019. - №20(1). P.60. doi: 10.1186/s12881-019-0790-2.Aboagye E.T., Adadey S.M., Wonkam-Tingang E. [et al.]. Global Distribution of Founder Variants Associated with Non-Syndromic Hearing Impairment. Genes. 2023; 14(2): 399. https://doi.org/10.3390/genes14020399Global Distribution of Founder Variants Associated with Non-Syndromic Hearing Impairment / E.T. Aboagye, S.M. Adadey, E. Wonkam-Tingang [et al.] // Genes. – 2023. №14(2). P.-399. https://doi.org/10.3390/genes14020399Petrova N., I.N. Tebieva N., Kadyshev V. [et al.]. Hereditary etiology of non-syndromic sensorineural hearing loss in the Republic of North Ossetia-Alani. Peer J. 2023; 11:e14514. doi: 10.7717/peerj.14514.Hereditary etiology of non-syndromic sensorineural hearing loss in the Republic of North Ossetia-Alania / N. Petrova, I. Tebieva, V. Kadyshev [et al.] // PeerJ. 2023 №11:e14514. doi: 10.7717/peerj.14514.Rehman A.U., Bird J.E., Faridi R. [et al.]. Mutational Spectrum of MYO15A and the Molecular Mechanisms of DFNB3 Human Deafness. Hum Mutat. 2016; 37(10): P.991-1003. doi: 10.1002/humu.23042.Mutational Spectrum of MYO15A and the Molecular Mechanisms of DFNB3 Human Deafness / A.U. Rehman, J.E. Bird, R. Faridi [et al.] // Hum Mutat. – 2016. №37(10). – P.991-1003. doi: 10.1002/humu.23042.Cengiz F.B., Duman D., Sirmaci A., [et al.]. Recurrent and private MYO15A mutations are associated with deafness in the Turkish population. Genetic Testing and Molecular Biomarkers. 2010; 14: 543–550. doi: 10.1089/gtmb.2010.0039.Recurrent and private MYO15A mutations are associated with deafness in the Turkish population / F.B. Cengiz, D. Duman, A. Sirmaci, [et al.] // Genetic Testing and Molecular Biomarkers. – 2010. №14. – P.543–550. doi: 10.1089/gtmb.2010.0039.Shatokhina O., Galeeva N., Stepanova A. [et al.]. Spectrum of Genes for Non-GJB2-Related Non-Syndromic Hearing Loss in the Russian Population Revealed by a Targeted Deafness Gene Panel. Int J Mol Sci. 2022; 23(24): 15748. doi: 10.3390/ijms232415748.Spectrum of Genes for Non-GJB2-Related Non-Syndromic Hearing Loss in the Russian Population Revealed by a Targeted Deafness Gene Panel / O. Shatokhina, N. Galeeva, A. Stepanova [et al.] // Int J Mol Sci. – 2022. №23(24). – P.15748. doi: 10.3390/ijms232415748.Manzoli G.N., Bademci G., Acosta A.X. [et al.]. Targeted Resequencing of Deafness Genes Reveals a Founder MYO15A Variant in Northeastern Brazil. Ann Hum Genet. 2016; 80(6): 327331. doi: 10.1111/ahg.12177.Targeted Resequencing of Deafness Genes Reveals a Founder MYO15A Variant in Northeastern Brazil / G.N. Manzoli, G. Bademci, A.X. Acosta [et al.] // Ann Hum Genet. – 2016. - №80(6). – P.327-331. doi: 10.1111/ahg.12177.Fang Q, Indzhykulian A.A., Mustapha M. [et al.]. The 133-kDa N-terminal domain enables myosin 15 to maintain mechanotransducing stereocilia and is essential for hearing. Elife. 2015; 24;4:e08627. doi: 10.7554/eLife.08627.The 133-kDa N-terminal domain enables myosin 15 to maintain mechanotransducing stereocilia and is essential for hearing / Q. Fang, A.A. Indzhykulian, M. Mustapha [et al.] // Elife. – 2015. №24;4:e08627. doi: 10.7554/ eLife.08627.Van Camp, G., Smith, R.J.H. Hereditary Hearing Loss Homepage. https://hereditaryhearingloss.org.Van Camp, G., Smith, R.J.H. Hereditary Hearing Loss Homepage. https://hereditaryhearingloss.org.Van Camp, G., Smith, R.J.H. Hereditary Hearing Loss Homepage. https://hereditaryhearingloss.org.

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