Leber’s hereditary optic neuropathy clinical features in patients with mitochondrial DNA m.13513G&gt;A candidate mutation

Andreeva, N.A.; Murakhovskaya, Yu.K.; Tsygankova, Polina G.; Крылова, Т.Д.; Sheremet, N L

doi:10.17116/oftalma2022138052208

Cited by 3 publications

(1 citation statement)

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“…In severe cases, clinical signs may manifest during the first two years, including the early neonatal period, while a lighter phenotype may develop in a childhood. Although in our series, early onset and severe neurological symptoms were noted in the patients with the m.8993T>C/G variant with high mutant load (>90%) for the m.13513G>A variant, we did not reveal strict genotype–phenotype correlations—among 12 patients with LS, the heteroplasmy in blood cells was 40–100% while in 5 patients with isolated LHON phenotype (not included in the study [ 17 ]), heteroplasmy overlapped strongly with LS patients (24–60%).…”

Section: Discussioncontrasting

confidence: 56%

Leigh Syndrome: Spectrum of Molecular Defects and Clinical Features in Russia

Denis

Tsygankova

Крылова

et al. 2023

IJMS

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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.

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Section: Discussioncontrasting

confidence: 56%