Whole exome sequencing identifies a novel homozygous MECR mutation in a Chinese patient with childhood-onset dystonia and basal ganglia abnormalities, without optic atrophy

Mitochondrion. 2021 Mar:57:222-229. doi: 10.1016/j.mito.2020.12.014. Epub 2021 Jan 2.

Abstract

Childhood-onset dystonia with optic atrophy and basal ganglia abnormalities is an extremely rare autosomal recessive mitochondrial disease caused by biallelic mutations in MECR. Using whole-exome sequencing, we identified a novel homozygous MECR mutation (c.910G > T, p.Asp304Tyr) in a Chinese patient with childhood-onset dystonia and basal ganglia abnormalities, without optic atrophy. With lipoic acid treatment, the disease progression was under control, and neither visual impairment nor optic atrophy was observed. To our knowledge, this is the first study about MECR-related mitochondrial disease in a Chinese patient and the first to report that supplementation with lipoic acid is a possible effective therapeutic strategy for this disease.

Keywords: Basal ganglia; Dystonia; Lipoic acid; MECR; Mitochondrial fatty acid synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Basal Ganglia / abnormalities*
  • Basal Ganglia / drug effects
  • Cells, Cultured
  • Child
  • China
  • Crystallography, X-Ray
  • Dystonia / diagnosis*
  • Dystonia / drug therapy
  • Dystonia / genetics
  • Dystonia / pathology
  • Exome Sequencing / methods*
  • Homozygote
  • Humans
  • Male
  • Models, Molecular
  • Mutation, Missense*
  • Oxidoreductases Acting on CH-CH Group Donors / chemistry
  • Oxidoreductases Acting on CH-CH Group Donors / genetics*
  • Pedigree
  • Protein Conformation
  • Thioctic Acid / administration & dosage
  • Thioctic Acid / pharmacology

Substances

  • Thioctic Acid
  • Oxidoreductases Acting on CH-CH Group Donors
  • trans-2-enoyl-CoA reductase (NADPH)