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

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.

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