medgenМедицинская генетикаMedical Genetics2073-7998Publishing House «Genius Media» LLC10.25557/2073-7998.2023.08.3-12medgen-2329Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL RESEARCHВариант m.1555A>G гена MT-RNR1 митохондриальной ДНК – основная причина потери слуха в Республике БурятияThe m.1555A>G variant of the MT-RNR1 gene of mitochondrial DNA is the main cause of hearing loss in the Republic of BuryatiaБорисоваТ. В.BorisovaT. V.

677000, г. Якутск, ул. Белинского, д. 58

58 Belinsky st., Yakutsk, 677000

ЧердоноваА. М.CherdonovaA. M.

677000, г. Якутск, ул. Белинского, д. 58

58 Belinsky st., Yakutsk, 677000

ПшенниковаВ. Г.PshennikovaV. G.

677000, г. Якутск, Ярославского 6/3

6/3 Yaroslavsky st., Yakutsk, 677018

ТерютинФ. М.TeruytinF. M.

677000, г. Якутск, Ярославского 6/3

6/3 Yaroslavsky st., Yakutsk, 677018

РомановГ. П.RomanovG. P.

677000, г. Якутск, ул. Белинского, д. 58

58 Belinsky st., Yakutsk, 677000

СоловьевА. В.SolovyevA. V.

677000, г. Якутск, ул. Белинского, д. 58

58 Belinsky st., Yakutsk, 677000

ФедороваС. А.FedorovaS. A.

677000, г. Якутск, Ярославского 6/3

6/3 Yaroslavsky st., Yakutsk, 677018

БарашковН. А.BarashkovN. A.

677000, г. Якутск, Ярославского 6/3

6/3 Yaroslavsky st., Yakutsk, 677018

barashkov2004@mail.ruФГАОУ ВО «Северо-Восточный федеральный университет им. М.К. Аммосова»РоссияNorth-Eastern Federal UniversityRussian FederationФГБНУ «Якутский научный центр комплексных медицинских проблем»РоссияYakut Science Centre of Complex Medical ProblemsRussian Federation202316102023228312Copyright © Борисова Т.В., Чердонова А.М., Пшенникова В.Г., Терютин Ф.М., Романов Г.П., Соловьев А.В., Федорова С.А., Барашков Н.А., 20232023Борисова Т.В., Чердонова А.М., Пшенникова В.Г., Терютин Ф.М., Романов Г.П., Соловьев А.В., Федорова С.А., Барашков Н.А.Borisova T.V., Cherdonova A.M., Pshennikova V.G., Teruytin F.M., Romanov G.P., Solovyev A.V., 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://www.medgen-journal.ru/jour/article/view/2329

Митохондриальные формы потери слуха составляют не более 1–2% среди всех несиндромальных случаев тугоухости и глухоты. Одним из наиболее распространенных каузативных вариантов митохондриального генома является m.1555A>G гена MT-RNR1, который ассоциирован с формой глухоты, индуцируемой антибиотиками аминогликозидного ряда (OMIM:561000). Внастоящее время вклад данной митохондриальной формы глухоты в этиологию потери слуха остается недостаточно изученным, поскольку детекция m.1555A>G гена MT-RNR1 входит не во все протоколы исследований. В настоящей работе методом ПЦРПДРФ анализа с последующим секвенированием по Сэнгеру впервые был проведен поиск патогенного варианта m.1555A>G гена MT-RNR1 у 165 пациентов с нарушениями слуха в Республике Бурятия. В результате, вариант m.1555A>G гена MT-RNR1 в состоянии гомоплазмии был обнаружен у 21 из 165 обследованных пациентов. Общий вклад m.1555A>G гена MT-RNR1 вэтиологию нарушений слуха вБурятии составил 12,7%, при этом высокая доля m.1555A>G гена MT-RNR1 выявлена у пациентов бурятов (20,2%) по сравнению с русскими пациентами (1,3%). Генетико-эпидемиологический анализ идентифицированной митохондриальной формы потери слуха в Бурятии выявил ее повышенную распространенность в трех районах на юге Республики, с максимальным накоплением в Джидинском муниципальном районе (4,5 на 10000). Анализ мировой распространенности варианта m.1555A>G гена MT-RNR1 среди 43435 пациентов с нарушением слуха показал, что его доля составляет в среднем 1,9%. Полученные результаты о высоком вкладе m.1555A>G гена MT-RNR1 в этиологию тугоухости и глухоты у пациентов бурятов свидетельствуют о том, что в регионе озера Байкал нами обнаружен один из наиболее крупных мировых очагов накопления митохондриальной формы потери слуха, который, вероятнее всего, обусловлен эффектом основателя.

Mitochondrial forms of hearing loss account for no more than 1-2% among all non-syndromic cases of hearing loss. However, one of the most common causative variants of the mitochondrial genome is m.1555A>G of the MT-RNR1 gene, which is associated with a deafness induced by aminoglycoside antibiotics (OMIM:561000). Currently, the contribution of the mitochondrial deafness to the etiology of hearing loss remains insufficiently studied, since the detection of the m.1555A>G of the MT-RNR1 gene is not included in all research protocols. In this work, using PCR-RFLP analysis followed by Sanger sequencing, the pathogenic variant m.1555A>G of the MT-RNR1 gene for the first time was searched in 165 hearing impaired patients in the Republic of Buryatia. As a result, the m.1555A>G of the MT-RNR1 gene in the homoplasmic state was detected in 21 out of 165 studied patients. The total contribution of the m.1555A>G (MT-RNR1 gene) to the etiology of hearing impairment in Buryatia was 12.7%. At the same time, a high proportion of m.1555A>G of the MT-RNR1 gene was detected in Buryat patients (20.2%), compared to Russian patients (1.3%). A genetic-epidemiological analysis of the identified mitochondrial form of hearing loss revealed its increased prevalence in three south districts in the Republic of Buryatia, with the maximum accumulation in the Dzhidinskii district (4.5 per 10,000 peoples). The analysis of the global prevalence of the variant m.1555A>G of the MT-RNR1 gene among 43435 patients with hearing impairment showed that its share is on average 1.9%. The results obtained on the high contribution of the m.1555A>G to the etiology of hearing impairment in Buryat patients indicate that we have found in the Baikal Lake region one of the largest of the world accumulation of the mitochondrial forms of hearing loss with most likely due to founder effect.

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