학술논문
Leigh Syndrome: Spectrum of Molecular Defects and Clinical Features in Russia.
Document Type
Academic Journal
Author
Kistol D; Research Centre for Medical Genetics, 115522 Moscow, Russia.; Tsygankova P; Research Centre for Medical Genetics, 115522 Moscow, Russia.; Krylova T; Research Centre for Medical Genetics, 115522 Moscow, Russia.; Bychkov I; Research Centre for Medical Genetics, 115522 Moscow, Russia.; Itkis Y; Research Centre for Medical Genetics, 115522 Moscow, Russia.; Nikolaeva E; Research and Clinical Institute of Pediatrics Named After Yuri Veltischev of the Pirogov Russian National Research Medical University of the Ministry of Health of the Russian Federation, 125412 Moscow, Russia.; Mikhailova S; Russian Children's Clinical Hospital, 119571 Moscow, Russia.; Sumina M; State Healthcare Institution of Sverdlovsk Region 'Clinical and Diagnostic Center 'Mother's and Child Health Protection', 620067 Ekaterinburg, Russia.; Pechatnikova N; Morozov Children's City Clinical Hospital, 119049 Moscow, Russia.; Kurbatov S; Research Institute of Experimental Biology and Medicine, Voronezh State Medical University Named after N. N. Burdenko, 394036 Voronezh, Russia.; Medical Center 'Zdorovii Rebenok', 394077 Voronezh, Russia.; Bostanova F; Research Centre for Medical Genetics, 115522 Moscow, Russia.; Migiaev O; Gemotest Laboratory LLC., 123112 Moscow, Russia.; Zakharova E; Research Centre for Medical Genetics, 115522 Moscow, Russia.
Source
Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
Subject
Language
English
Abstract
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.