Leigh syndrome (LS), also known as infantile subacute necrotizing encephalopathy, is the most frequent mitochondrial disorder in children. Recently, more than 80 genes have been associated with LS, which greatly complicates the diagnosis. In this article, we present clinical and molecular findings of 219 patients with LS and give the detailed description of three cases with rare findings in nuclear genes MORC2, NARS2 and VPS13D, demonstrating wide genetic heterogeneity of this mitochondrial disease. The most common cause of LS in Russian patients are pathogenic variants in the SURF1 gene (44.3% of patients). The most frequent pathogenic variant is c.845_846delCT (66.0% of mutant alleles; 128/192), which is also widespread in Eastern Europe. Five main LS genes, SURF1, SCO2, MT-ATP6, MT-ND5 and PDHA1, account for 70% of all LS cases in the Russian Federation. Using next generation sequencing (NGS) technique, we were able to detect pathogenic variants in other nuclear genes: NDUFV1, NDUFS2, NDUFS8, NDUFAF5, NDUFAF6, NDUFA10, SUCLG1, GFM2, COX10, PMPCB, NARS2, PDHB and SLC19A3, including two genes previously associated with Leigh-like phenotypes—MORC2 and VPS13D. We found 49 previously undescribed nucleotide variants, including two deep intronic variants which affect splicing.
АннотацияВ обзоре представлены отечественные и зарубежные данные, отражающие особенности медико-генетического консультирования и прогностического тестирования пациентов с наследственными заболеваниями сердечно-сосудистой системы. Освещены этические проблемы геномного тестирования, особенно вторичных (случайных) находок, каскадного скрининга, обследования детей и подростков, посмертного генетического тестирования. Особое внимание уделено психосоциальному воздействию генетического тестирования. Ключевые слова:наследственные сердечно-сосудистые заболевания, генетическое консультирование, секвенирование ДНК, каскадный скрининг. Конфликт интересов:авторы заявляют об отсутствии конфликта интересов. Прозрачность финансовой деятельности:исследование выполнено за счет гранта Российского научного фонда (проект № 19-18-00422).
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