Novel MECR mutation in a Czech patient with childhood-onset dystonia, optic atrophy, and basal ganglia abnormality
Abstrakt
Background/Objectives: Gene MECR encodes a highly conserved mitochondrial trans-2-enoyl-coenzyme-A-reductase which has a crucial role in mitochondrial fatty acid synthesis (mFAS). Here we report a 12-year-old patient with recessive mutations in MECR who presented with childhood-onset dystonia, hypoplasia and atrophy of the optical nerves, and abnormal MRI signaling of basal ganglia and dorsal mesencephalon.
Methods: Family-based whole-exome sequencing of DNA extracted from peripheral blood lymphocytes was followed by bioinformatics analysis of the TRIO using the software VarAFT. Functional measurement of mitochondrial oxidative phosphorylation (OXPHOS) were performed on skin fibrocytes via highresolution respirometry (OroborosOxygraph).
Western blot was used to detect individual mitochondrial proteins and to study the assembly of OXPHOS complexes. Results: Within gene MECR, we found a novel variant c.610G>C p.(Ala204Pro) and previously described variant c.772C>T p.(Arg258Trp) in a compound heterozygous state.
Functional measurements of OXPHOS on fibrocyte cell line found a statistically significant decrease of the mitochondrial electron transport chain (ETC) capacity, complex I and IV capacity, and overall mild decrease of respiration. Western blot showed a decreased quantity of complexes I and IV.
Conclusion: We described a novel variant c.610G>C in MECR in an individual with a phenotype consistent with previously described cases of the MECR-related neurologic disorder (1). The pathogenicity of the variant was confirmed by functional analysis