Гетеротаксический синдром: генетические факторы (обзор литературы)

Синдром гетеротаксии, как правило, сопровождается врожденными пороками сердца, которые преимущественно определяют тяжесть состояния пациента и высокую летальность, доходящую до 80% на первом году жизни. В ряде случаев гетеротаксия обусловлена хромосомной и генной патологией, которая активно изучается последние десятки лет. По данным литературы, встречаемость патогенных вариаций числа копий (pCNVs) при этой аномалии оценивается в 15-20%, а моногенных вариантов – 10-20%. Целью данного исследования является анализ работ последних 10 лет, где представлены результаты генетических исследований пациентов с нарушениями латеральности, и суммирование найденных находок для выявления наиболее перспективных методов диагностики. Был проведен электронный поиск по базам данных PubMed и E-library работ, где применялись кариотипирование, определение CNV и секвенирование экзома. Суммарно из 1357 пациентов с гетеротаксией, обследованных различными методами в обозреваемых работах, предполагаемая генетическая причина определена у 278 человек, что составило 20,5%. Кариотипирование 56 пациентов не выявило случаев анеуплоидии. Поиск pCNV проводился у 154 человек, преимущественно методом хромосомного микроматричного анализа (ХМА), что привело к выявлению анеуплоидий у 4,5% обследованных и микроструктурных патологических перестроек у 6,5%. Секвенирование экзома применялось у 1147 пациентов с гетеротаксией, и в 22,8% случаев были определены патогенные или вероятно патогенные генетические варианты. Более предпочтительным методом диагностики является ХМА, в связи с более тяжелой клиникой гетеротаксического синдрома, сочетающегося с микроструктурными хромосомными повреждениями, и возможностью его применения на пренатальном этапе. Секвенирование экзома рекомендовано в качестве второго этапа для заключения о риске повторения гетеротаксии при дальнейшем деторождении.

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