Analysis of pathogenic variants of the mtDNA MT-TS1 gene in patients with hearing loss in Buryatia
https://doi.org/DOI10.25789/YMJ.2023.84.01
Abstract
In this work we searched for pathogenic variants of the mtDNA MT-TS1 gene in patients with hearing impairments in Buryatia. One rare variant m.7445A>C was found in the MT-TS1 gene out of five investigated variants in one patient (1/165; 0.6%). This variant is localized in the coding region of two genes the MT-CO1 (H-chain) and MT-TS1 (L-chain), but on different mtDNA chains. However, a pathogenetic role for the m.7445A>C substitution has been shown for the MT-TS1 gene, but not for the MT-CO1 gene. In databases, the m.7445A>C variant is associated with non-syndromic hearing loss, including those caused by aminoglycoside antibiotics. A comparative genotype-phenotypic analysis of our case and four cases with m.7445A>C of the MT-TS1 gene described earlier in the literature showed that hearing loss in all cases is not congenital, but at the same time varies in severity with low penetrance. The results obtained indicate the involvement of other modulating factors in the clinical manifestation of hearing impairment associated with this variant. Thus, further study of rare variants of MT-TS1 gene will contribute to our understanding of the pathogenetic mechanisms of mitochondrial forms of hearing loss.
Supporting agencies: This work was carried out within the framework of the State Assignment of the Ministry of Science and Higher Education of the Russian Federation (FSRG-2023- 0003).
About the Authors
T. V. Borisova
M. Ammosov Northeastern Federal University
Russian Federation
Russian Federation
Borisova Tuara Valeryevna – post-graduate student
Yakutsk
A. M. Cherdonova
M. Ammosov Northeastern Federal University
Russian Federation
Russian Federation
Cherdonova Alexandra Anatolyevna – post-graduate student
Yakutsk
G. P. Romanov
M. Ammosov Northeastern Federal University
Russian Federation
Russian Federation
Romanov Georgy Prokopievich – research assistant
Yakutsk
A. V. Solovyov
M. Ammosov Northeastern Federal University
Russian Federation
Russian Federation
Solovyov Aisen Vasilyevich – PhD in Biology, senior researcher
Yakutsk
V. G. Pshennikova
Yakut Scientific Center of Complex Medical Problems
Russian Federation
Russian Federation
Pshennikova Vera Gennadievna – PhD in Biology, visiting scholar
F. M. Teryutin
Yakut Scientific Center of Complex Medical Problems
Russian Federation
Russian Federation
Teryutin Fyodor Mikhailovich - – PhD, Senior Researcher
N. A. Barashkov
Yakut Scientific Center of Complex Medical Problems
Russian Federation
Russian Federation
Barashkov Nikolay Alekseevich – PhD in Biology, visiting scholar
S. A. Fedorova
M. Ammosov Northeastern Federal University
Russian Federation
Russian Federation
Fedorova Alexandra Arkadyevna – Doctor of Biology, chief researcher
Yakutsk
References
1. Analysis of 12S rRNA and tRNASer(UCN) mtDNA genes in patients with nonsyndromic sensorineural hearing loss/deafness from various regions of Russia / L.U. Dzhemileva, O.L. Posukh, A.M. Tazetdinov [et al.] // Genetics. 2009. Vol. 45, No. 7. P. 982-991.
2. A deafness-associated mitochondrial DNA mutation altered the tRNASer(UCN) metabolism and mitochondrial function / L. Xue, Y. Chen, X. Tang [et al.] // Mitochondrion. – 2019. – 46. – P.370-379. doi: 10.1016/j.mito.2018.10.001.
3. A novel mitochondrial point mutation in a maternal pedigree with sensorineural deafness / F.M. Reid, G.A. Vernham, H.T. Jacobs // Hum Mutat. – 1994. – 3(3). – P. 243-7. doi: 10.1002/humu.1380030311.
4. DFNB1 Non-Syndromic Hearing Impairment: Diversity of Mutations and Associated Phenotypes / F.J. Del Castillo, I. del Castillo // Front. Mol. Neurosci. – 2017. – 10. – P.428.
5. 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(1). – P.27-35. doi: 10.1086/301676.
6. Genetic epidemiological studies of early-onset deafness in the U.S. school-age population / M. L. Marazita, L. M. Ploughman, B. Rawlings [et al.] // Am.J.Med.Genet. – 1993. – 46. – P. 486–491.
7. Genetic etiology of non-syndromic hearing loss in Europe / I. Del Castillo, M. Morín, M. Domínguez-Ruiz, M.A. Moreno-Pelayo // Hum Genet. – 2022. – 141(3-4). – P.683-696. doi: 10.1007/s00439-021-02425-6.
8. Heterogenous point mutations in the mitochondrial tRNA Ser(UCN) precursor coexisting with the A1555G mutation in deaf students from Mongolia / A. Pandya, X.J. Xia, R. Erdenetungalag [et al.] // Am J Hum Genet. – 1999. – 65(6). - P.1803-6. doi: 10.1086/302658.
9. In vitro 3'-end endonucleolytic processing defect in a human mitochondrial tRNA(Ser(UCN)) precursor with the U7445C substitution, which causes non-syndromic deafness / L. Levinger, O. Jacobs, M. James // Nucleic Acids Res. – 2001. – 1;29(21). – P.4334-40. doi: 10.1093/nar/29.21.4334.
10. Mitochondrial mutation associated with nonsyndromic deafness / N. Fischel-Ghodsian, T.R. Prezant, P. Fournier [et al.] // Am J Otolaryngol. – 1995. – 16(6). – P.403-8. doi: 10.1016/0196-0709(95)90078-0.
11. Mitochondrial tRNA 3' end metabolism and human disease / L. Levinger, M. Mörl, C. Florentz // Nucleic Acids Res. – 2004. – 11;32(18). – P.5430-41. doi: 10.1093/nar/gkh884.
12. Mitochondrial tRNA mutations in 887 Chinese subjects with hearing loss / J. Zheng, X. Bai, Y. Xiao [et al.] // Mitochondrion. – 2020. – 52. – P.163-172. doi: 10.1016/j.mito.2020.03.005.
13. Mitochondrial tRNA(Ser(UCN)) variants in 2651 Han Chinese subjects with hearing loss / X. Tang, J. Zheng, Z. Ying [et al.] // Mitochondrion. – 2015. – 23. – P.17-24. doi: 10.1016/j.mito.2015.05.001.
14. Mitochondrial tRNASer(UCN) gene is the hot spot for mutations associated with aminoglycoside-induced and non-syndromic hearing loss / L. Jin, A. Yang, Y. Zhu [et al.] // Biochem Biophys Res Commun. – 2007. – 14;361(1). – P.133- 9. doi: 10.1016/j.bbrc.2007.06.171.
15. mtDNA variation and analysis using MITOMAP and MITOMASTER / M.T. Lott, J.N. Leipzig, O. Derbeneva [et al.] // Current Protocols in Bioinformatics. – 2013. – 44(123). – P.1.23.1-26. PMID: 25489354 URL: http://www.mitomap.org
16. 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 [et al.] // Am J Hum Genet. – 2006. – 79(2). – P.291-302. doi: 10.1086/506389.
17. Mutations at position 7445 in the precursor of mitochondrial tRNASer(UCN) gene in three maternal Chinese pedigrees with sensorineural hearing loss / J. Chen, H. Yuan, J. Lu [et al.] // Mitochondrion. – 2008. – 8(4). – P.285-92. doi: 10.1016/j.mito.2008.05.002.
18. Newborn Hearing Screening - A Silent Revolution / P.C. Morton, W.E. Nance // New England Journal of Medicine. - 2006. - №20(354). - P. 2151–2164. doi: 10.1056/NEJMra050700.
19. Prevalence of mitochondrial DNA mutations in childhood/congenital onset non-syndromal sensorineural hearing impairment / T.P. Hutchin, K.R. Thompson, M. Parker [et al.] // J Med Genet. – 2001. – 38(4). – P.229-31. doi: 10.1136/jmg.38.4.229.
20. 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. – P.15748. https://doi.org/10.3390/ijms232415748.
21. The deafness-associated mitochondrial DNA mutation at position 7445, which affects tRNASer(UCN) precursor processing, has longrange effects on NADH dehydrogenase subunit ND6 gene expression / M.X. Guan, J.A. Enriquez, N. Fischel-Ghodsian [et al.] // Mol Cell Biol. – 1998. – 18(10). – P.5868-79. doi: 10.1128/MCB.18.10.5868.
22. Usami S.I., Nishio S.Y. Nonsyndromic Hearing Loss and Deafness, Mitochondrial. 2004 Oct 22 [updated 2018 Jun 14] / M.P. Adam, D.B. Everman, G.M. Mirzaa [et al.] editors // GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; – 1993–2023. PMID: 20301595. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1422/
23.
Review
For citations:
Borisova T.V., Cherdonova A.M., Romanov G.P., Solovyov A.V., Pshennikova V.G., Teryutin F.M., Barashkov N.A., Fedorova S.A. Analysis of pathogenic variants of the mtDNA MT-TS1 gene in patients with hearing loss in Buryatia. Yakut Medical Journal. 2023;(4):5-9. https://doi.org/DOI10.25789/YMJ.2023.84.01
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