Формирование когнитивных процессов у детей с аутизмом. Часть I. Эпигенетические механизмы

   Аутизм и расстройства аутистического спектра — нервно-психические заболевания, которые начинают проявляться у детей в возрасте до 3 лет. За последнее десятилетие число детей с расстройствами аутистического спектра увеличилось в 10 раз и продолжает расти, составляя 1–2 % населения планеты. В настоящее время диагностика расстройств аутистического спектра основывается только на клинических и поведенческих тестах, а биологические и генетические маркеры, которые могли бы способствовать раннему выявлению этого расстройства, отсутствуют. В обзоре на основе анализа современных данных литературы об эпигенетических механизмах, ассоциированных с аутизмом, рассматриваются влияние профиля метилирования ДНК на формирование когнитивных нарушений и возможность использования статуса метилирования генов в качестве диагностических биомаркеров у детей с расстройствами аутистического спектра. Анализ данных литературы свидетельствует, что в основе нарушений внимания, скорости обработки информации, рабочей памяти, обучения лежат генетические и эпигенетические (метилирование) изменения экспрессии многих генов: BDNF, CAPS2, CNTNAP2, GABRB3, FMR1, FOXP1, GTF2I, HSD11B2, MECP2, NF2, NGF, NR3C1, OXTR, PAK2, RELN, SLC6A4, UBE3A и др. Большинство из этих генов подвергается гиперметилированию, уменьшая экспрессию их белков, что нарушает развитие и формирование нервной системы при аутизме. Напротив, другие гены, ассоциированные с метилированием и окислительным стрессом, гипометилированы при расстройствах аутистического спектра. Оценка уровня экспрессии и статуса метилирования этих генов может служить генетическими и эпигенетическими биомаркерами для дифференциации и диагностики клинических симптомов, тяжести расстройства аутистического спектра, а также способствовать разработке новых методов лечения и реабилитационных процедур.

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