References

medgen

Медицинская генетика

Medical Genetics

2073-7998

Publishing House «Genius Media» LLC

10.25557/2073-7998.2023.07.51-60

medgen-2328

Research Article

ОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯ

ORIGINAL RESEARCH

Анализ гена SLC26A4 и его генетического окружения у пациентов с нарушениями слуха и расширенным водопроводом преддверия в Бурятии

Analysis of the SLC26A4 gene including its genetic background in patients with hearing impairments and an enlarged vestibular aqueduct from Buryatia

Чердонова

А. М.

Cherdonova

A. M.

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

58 Belinsky st., Yakutsk, 677000

Борисова

Т. В.

Borisova

T. V.

677000, г. Якутск, ул. Ярославского, д. 6/3

6/3 Yaroslavsky st., Yakutsk, 677018

Пшенникова

В. Г.

Pshennikova

V. G.

677000, г. Якутск, ул. Ярославского, д. 6/3

6/3 Yaroslavsky st., Yakutsk, 677018

Терютин

Ф. М.

Teryutin

F. M.

677000, г. Якутск, ул. Ярославского, д. 6/3

6/3 Yaroslavsky st., Yakutsk, 677018

Кларов

Л. А.

Klarov

L. A.

677000, г. Якутск, ул. Ярославского, д. 6/3

6/3 Yaroslavsky st., Yakutsk, 677018

Никанорова

А. А.

Nikanorova

A. A.

677000, г. Якутск, ул. Ярославского, д. 6/3

6/3 Yaroslavsky st., Yakutsk, 677018

Романов

Г. П.

Romanov

G. P.

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

58 Belinsky st., Yakutsk, 677000

Соловьев

А. В.

Solovyev

A. V.

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

58 Belinsky st., Yakutsk, 677000

Федорова

С. А.

Fedorova

S. A.

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

58 Belinsky st., Yakutsk, 677000

Барашков

Н. А.

Barashkov

N. A.

677000, г. Якутск, ул. Ярославского, д. 6/3

6/3 Yaroslavsky st., Yakutsk, 677018

barashkov2004@mail.ru

ФГАОУ ВО «Северо-Восточный федеральный университет им. М.К. Аммосова»РоссияNorth-Eastern Federal UniversityRussian Federation

ФГБНУ «Якутский научный центр комплексных медицинских проблем»РоссияYakut Science Centre of Complex Medical ProblemsRussian Federation

2023

16102023

2275160

2023

Чердонова А.М., Борисова Т.В., Пшенникова В.Г., Терютин Ф.М., Кларов Л.А., Никанорова А.А., Романов Г.П., Соловьев А.В., Федорова С.А., Барашков Н.А.

Cherdonova A.M., Borisova T.V., Pshennikova V.G., Teryutin F.M., Klarov L.A., Nikanorova A.A., 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/2328

Патогенные варианты гена SLC26A4 ассоциированы как с аутосомно-рецессивной глухотой 4 типа (DFNB4, OMIM #600791), так и с синдромом Пендреда (PS, OMIM #274600). В настоящей работе проведен поиск каузативных вариантов гена SLC26A4 и анализ его генетического окружения (гаплотип CEVA) у шести пациентов из Бурятии с нарушениями слуха и расширенным водопроводом преддверия (EVA), которые в части случаев были сочетаны с кистозными аномалиями улитки (IP-1 и IP-2) и с нарушением тиреоидной функции. Исследование включало клинико-аудиологический анализ порогов слуха, компьютерную томографию височных костей, анализ гормонов гипофизарно-тиреоидной системы (ТТГ, св.Т3 и св.Т4), прямое секвенирование по Сэнгеру кодирующих районов гена SLC26A4 (21 экзон) и генотипирование 12 SNP-маркеров, составляющих гаплотип CEVA. Вцелом, уобследованных пациентов доля SLC26A4 биаллельных (M2) и моноаллельных случаев в сочетании с CEVA-гаплотипом в транс-положении (M1+CEVA) составила 83,3% (5 из 6 пациентов). При этом, у пациентов бурятов доля случаев с M2 составила 100% (3 из 3 пациентов), в то время как у русских пациентов доля случаев с М2 и М1+CEVA составила 66,6% (2 из 3 пациентов). Высокий мутационный вклад гена SLC26A4 у пациентов бурятов может быть связан с распространенностью в регионе озера Байкал мажорных вариантов этого гена c.919-2A>G (IVS7-2A>G) и c.2027T>A p.(Leu676Gln), характерных для ряда регионов Сибири и Восточной Азии. Идентификация гаплотипа CEVA в транс-положении у одного русского пациента с моноаллельным вариантом гена SLC26A4 (М1+CEVA), свидетельствует об актуальности дальнейшей оценки диагностической значимости CEVA-гаплотипа в когортах российских пациентов с нарушениями слуха.

Pathogenic variants of the SLC26A4 gene are associated with both autosomal recessive deafness type 4 (DFNB4, OMIM #600791) and Pendred syndrome (PS, OMIM #274600). In this work, we searched for causative variants of the SLC26A4 gene and its genetic background (CEVA haplotype) in six patients in Buryatia with hearing impairments and an enlarged vestibular aqueduct (EVA), which in some cases was combined with cystic cochlear anomalies (IP-1 and IP-2) and with impaired thyroid function. The study included clinical and audiological analyses of hearing thresholds, computed tomography of the temporal bones, analysis of hormones of the hypothalamic– pituitary–thyroid axis (TSH, free T3 and free T4), direct Sanger sequencing of the coding regions of the SLC26A4 gene (21 exons) and genotyping of 12 SNPs markers of the CEVA haplotype. In general, among the studied patients, the proportion of SLC26A4 biallelic (M2) and monoallelic cases in combination with the CEVA haplotype in trans-position (M1+CEVA) was 83.3% (5 of 6 cases). At the same time, in Buryat patients, the proportion of cases with M2 was 100% (3 out of 3 cases), while in Russian patients, the proportion of cases with M2 and M1 + CEVA was 66.6% (2 out of 3 cases). The high contribution of the SLC26A4 gene in Buryat patients may be associated with the prevalence of the major variants of this gene c.919-2A>G (IVS7-2A>G) and c.2027T>A p.(Leu676Gln) common for regions of Siberia and Eastern Asia. Identification of the CEVA haplotype in trans-position in one Russian patient with a monoallelic variant of the SLC26A4 gene (M1+CEVA) indicates the relevance of further assessment of the diagnostic significance of the CEVA haplotype in cohorts of Russian patients with hearing impairments.

потеря слухааномалии внутреннего ухарасширение водопровода преддверия (EVA)неполное разделение улитки (IP-1 и IP-2)нарушение тиреоидной функциисиндром Пендредаген SLC26A4CEVA-гаплотипБурятия

hearing lossinner ear anomaliesenlarged vestibular aqueduct (EVA)incomplete partition of the cochlea (IP-1 and IP-2)thyroid dysfunctionPendred syndromeSLC26A4 geneCEVA haplotypeBuryatia

Работа 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).

This work was supported by research work of the YSC CMP “Study of the genetic structure and burden of hereditary pathology in the populations of the Republic of Sakha (Yakutia)” and the Ministry of Science and Higher Education of the Russian Federation (FSRG-2023-0003).

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