ymjЯкутский медицинский журналYakut Medical Journal1813-19052312-1017ЯНЦ КМП10.25789/YMJ.2023.84.01ymj-213Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL RESEARCHПоиск патогенных вариантов гена MT-TS1 мтДНК у пациентов с нарушениями слуха в БурятииAnalysis of pathogenic variants of the mtDNA MT-TS1 gene in patients with hearing loss in BuryatiaБорисоваТ. В.BorisovaT. V.

Борисова Туяра Валерьевна – аспирант

 г. Якутск

Borisova Tuara Valeryevna – post-graduate student

Yakutsk

borisovatv96@gmail.comЧердоноваА. М.CherdonovaA. M.

Чердонова  Александра Матвеевна – аспирант

г. Якутск

Cherdonova Alexandra Anatolyevna – post-graduate student

Yakutsk

cherdonovasasha96@gmail.comРомановГ. П.RomanovG. P.

Романов  Георгий Прокопьевич – н.с.г. Якутск

Romanov  Georgy Prokopievich – research assistant

Yakutsk

gpromanov@gmail.comСоловьевА. В.SolovyovA. V.

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

г. Якутск

Solovyov Aisen Vasilyevich – PhD in Biology, senior researcher

Yakutsk

nelloann@mail.ruПшенниковаВ. Г.PshennikovaV. G.

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

Pshennikova Vera Gennadievna – PhD in Biology, visiting scholar

psennikovavera@mail.ruТерютинФ. М.TeryutinF. M.

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

 Teryutin  Fyodor Mikhailovich - – PhD, Senior Researcher

rest26@mail.ruБарашковН. А.BarashkovN. A.

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

Barashkov Nikolay Alekseevich – PhD in Biology, visiting scholar

barashkov2004@mail.ruФедороваС. А.FedorovaS. A.

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

г. Якутск

Fedorova Alexandra Arkadyevna – Doctor of Biology, chief researcher

Yakutsk

sardaanafedorova@mail.ruФГАОУ ВО «Северо-Восточный федеральный университет им. М.К. Аммосова»РоссияM. Ammosov Northeastern Federal UniversityRussian FederationФГБНУ «Якутский научный центр комплексных медицинских проблем»РоссияYakut Scientific Center of Complex Medical ProblemsRussian Federation2023050220250459Copyright © Борисова Т.В., Чердонова А.М., Романов Г.П., Соловьев А.В., Пшенникова В.Г., Терютин Ф.М., Барашков Н.А., Федорова С.А., 20252025Борисова Т.В., Чердонова А.М., Романов Г.П., Соловьев А.В., Пшенникова В.Г., Терютин Ф.М., Барашков Н.А., Федорова С.А.Borisova T.V., Cherdonova A.M., Romanov G.P., Solovyov A.V., Pshennikova V.G., Teryutin F.M., Barashkov N.A., Fedorova S.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/213

Проведен поиск патогенных вариантов гена MT-TS1 мтДНК у пациентов с нарушениями слуха в Бурятии. В результате исследования в гене MT-TS1 из пяти исследованных патогенных вариантов, обуславливающих нарушение слуха, был обнаружен вариант m.7445A>C у одной пациентки. Данный вариант локализован в кодирующей области двух генов MT-CO1 (H-цепь) и MT-TS1 (L-цепь), но на разных цепях мтДНК. Однако патогенетическая роль замены m.7445A>C показана только для гена MT-TS1. В базах данных замена m.7445A>C ассоциирована с несиндромальной тугоухостью, в том числе вызванной антибиотиками аминогликозидного ряда. Сравнительный генотип-фенотипический анализ нашего случая и описанных ранее в литературе четырех случаев с m.7445A>C гена MT-TS1 показал, что потеря слуха во всех случаях не является врожденной, но при этом варьирует по степени тяжести с низкой пенетрантностью. Полученные результаты свидетельствуют о вероятном участии других модулирующих факторов в клиническом проявлении нарушений слуха, ассоциированных с данным вариантом. Таким образом, дальнейшее изучение редких вариантов гена MT-TS1 будет способствовать пониманию патогенетических механизмов митохондриальных форм потери слуха.

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.

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