Молекулярно-генетическая характеристика гипогидротических эктодермальных дисплазий

Эктодермальные дисплазии – гетерогенная группа наследственных заболеваний кожи и ее придатков, которые характеризуются нарушением развития и/или гомеостаза двух и более производных эктодермы, включая: волосы, зубы, ногти, потовые железы и их модификации (например, молочные железы). Общая распространенность эктодермальных дисплазий остается точно неизвестной не только в России, но и в мире, так же как и вклад отдельных генов в ее структуру. Это затрудняет ДНК-диагностику данного заболевания ввиду отсутствия строгого алгоритма диагностики и универсального, экономически выгодного метода анализа. На сегодняшний день наиболее изученными генами, вовлеченными в развитие ангидротической или гипогидротической форм эктодермальной дисплазии являются EDA, EDAR, EDARADD и WNT10A. Ген эктодисплазина А (EDA) служит причиной самой частой Х-сцепленной формы эктодермальной дисплазии, ген из семейства Wnt (WNT10A) отвечает за аутосомно-рецессивную форму заболевания, а два других гена (EDAR и EDARADD) могут быть причиной как аутосомно-рецессивных, так и аутосомно-доминантных форм. В настоящем литературном обзоре приведены характеристика генов, вовлеченных в эктодермальную дисплазию, спектры их мутаций, уровень их экспрессии в тканях человека, а также взаимосвязь вышеупомянутых генов друг с другом. Обсуждается также доменная структура соответствующих белков, рассмотрены молекулярногенетические пути, в которые они преимущественно вовлечены, и описаны животные модели для изучения данной патологии. Ввиду межвидовой консервативности упомянутых генов, мутации в них вызывают нарушения развития производных эктодермы не только у человека, но и у мышей, коров, собак и даже рыб, что может быть использовано для лучшего понимания этиопатогенеза эктодермальных дисплазий. Более того, в статье поднимаются вопросы о возможных частых мутациях в генах EDA и WNT10A. Приведены также данные касаемо разрабатываемых перспективных подходов к внутриутробному лечению эктодермальной дисплазии.

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