Клиническая интеграция генетической диагностики в педиатрическую нефрологию. Обзор литературы

Наследственные заболевания почек являются одной из ведущих причин хронической болезни почек в детском возрасте. Диагностика генетически-ассоциированных заболеваний почек на клиническом уровне нередко сложна вследствие выраженной генетической гетерогенности патологии и клинического полиморфизма проявлений. В последние годы в клинической практике применяется массовое параллельное секвенирование, разновидностью которого являются методы секвенирования нового поколения. Современное генетическое тестирование привело к улучшению диагностики генетически гетерогенных заболеваний, идентификации новых генов, что способствовало значительному прогрессу в понимании патогенетических механизмов, выявлению ранее нераспознанных фенотипов, а также реклассификации ряда заболеваний почек, включая COL4A-ассоциированную гломерулопатию и аутосомно-доминантные тубуло-интерстициальные заболевания почек. В обзоре представлены различные типы наследования моногенных заболеваний на примере патологии почек, сгруппированные из медицинской базы данных OMIM. Приводятся литературные сведения о современных молекулярно-генетических и цитогенетических методах диагностики, включая секвенирование по Сэнгеру, таргетные мультигенные панели, технологии массового параллельного секвенирования экзома и генома, а также хромосомный микроматричный анализ. Освещены в сравнительном аспекте преимущества и ограничения молекулярно-генетических методов диагностики. Представлены показания к генетическому обследованию при подозрении на наследственный характер патологии почек, обращается внимание на необходимость интерпретации данных генетических исследований в соответствие с международными и российскими рекомендациями профессиональных сообществ медицинских генетиков. В статье приводится алгоритм генетической диагностики с примерами клинического применения в нефрологической практике, включая обоснованные диагностические и терапевтические подходы. Представлены клинические ситуации, при которых проведение генетического тестирования может позволить пациентам избежать избежать нефробиопсии или иммуносупрессивной терапии с потенциальными побочными эффектами. Показано, что применение генетических методов исследования в педиатрической нефрологии является необходимым диагностическим инструментом для поиска причин наследственных заболеваний, выбора фармакотерапии, прогнозирования течения заболевания, а также медико-генетического консультирования семей пациентов и пренатальной диагностики наследственных заболеваний.

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