medgenМедицинская генетикаMedical Genetics2073-7998Publishing House «Genius Media» LLC10.25557/2073-7998.2024.02.14-26medgen-2418Research ArticleНАУЧНЫЙ ОБЗОРREVIEWГетеротаксический синдром: генетические факторы (обзор литературы)Heterotaxy syndrome: genetic factors (review)ФеденевС. Н.FedenevS. N.

620028, г. Екатеринбург, ул. Репина, д. 3

3, Repina st., Yekaterinburg, 620028

s.n.fedenev@yandex.ruКудрявцеваЕ. В.KudryavtsevaE. V.

620028, г. Екатеринбург, ул. Репина, д. 3

620067, г. Екатеринбург, ул. Флотская, д. 52

620026, г. Екатеринбург, ул. Карла Маркса, д. 22а

3, Repina st., Yekaterinburg, 620028

52, Flotskaya st., Yekaterinburg, 620067

22A, Karla Marksa st., Yekaterinburg, 620026

КовалевВ. В.KovalevV. V.

620028, г. Екатеринбург, ул. Репина, д. 3

3, Repina st., Yekaterinburg, 620028

МостоваН. В.MostovaN. V.

620026, г. Екатеринбург, ул. Карла Маркса, д. 22а

22A, Karla Marksa st., Yekaterinburg, 620026

СтрюковаК. В.StyukovaK. V.

620028, г. Екатеринбург, ул. Репина, д. 3

3, Repina st., Yekaterinburg, 620028

ФГБОУ ВО Уральский государственный медицинский университет Минздрава РоссииРоссияUral State Medical University of the Ministry of Health of the Russian FederationRussian FederationФГБОУ ВО Уральский государственный медицинский университет Минздрава России; ГАУЗ СО «Клинико-диагностический центр «Охрана здоровья матери и ребенка»»; ГАУЗ СО «Институт медицинских клеточных технологий»РоссияUral State Medical University of the Ministry of Health of the Russian Federation; Clinical and Diagnostic Center Maternal and Child Health Protection; Institute of Medical Cell TechnologiesRussian FederationГАУЗ СО «Институт медицинских клеточных технологий»РоссияInstitute of Medical Cell TechnologiesRussian Federation2024250320242321426Copyright © Феденев С.Н., Кудрявцева Е.В., Ковалев В.В., Мостова Н.В., Стрюкова К.В., 20242024Феденев С.Н., Кудрявцева Е.В., Ковалев В.В., Мостова Н.В., Стрюкова К.В.Fedenev S.N., Kudryavtseva E.V., Kovalev V.V., Mostova N.V., Styukova K.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.medgen-journal.ru/jour/article/view/2418

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.

Heterotaxy syndrome is usually accompanied by congenital heart defects, which predominantly determine the severity of the patient’s condition and the high mortality rate, reaching up to 80% in the first year of life. In some cases, heterotaxy is caused by chromosomal and genetic abnormalities, which have been actively studied in recent decades. According to literature data, the prevalence of pathogenic copy number variations (pCNVs) in this anomaly is estimated at 15-20%, while monogenic variants account for 10-20%. The aim of this study is to analyze the work of the past 10 years, which includes the results of genetic studies on patients with laterality disorders, and to summarize the findings to identify the most promising diagnostic methods. An electronic search was conducted using the PubMed and E-library databases, where techniques such as karyotyping, CNV determination, and exon sequencing were applied. In total, out of 1357 patients with heterotaxy who were examined by various methods in the reviewed studies, a suspected genetic cause was identified in 278 individuals, accounting for 20.5%. Karyotyping among 56 patients did not reveal any cases of aneuploidy. The search for pCNVs was conducted on 154 individuals, predominantly using array comparative genomic hybridization (aCGH), which resulted in the detection of aneuploidies in 4.5% of the subjects and pathogenic microstructural chromosomal rearrangements in 6.5%. Exome sequencing was performed on 1147 patients with heterotaxy, and pathogenic or likely pathogenic genetic variants were identified in 22.8% of cases. aCGH is considered a preferred diagnostic method due to the more severe clinical presentation of heterotaxy syndrome, which is often associated with microstructural chromosomal abnormalities, and its potential application in the prenatal stage. Exome sequencing is recommended as a second step for assessing the risk of heterotaxy recurrence in future pregnancies.

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The authors declare that there are no conflicts of interest present.