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

Zhimei Liu; Masaru Shimura; Li Zhang; Weihua Zhang; Jianing Wang; Minako Ogawa-Tominaga; Junling Wang; Xiaohui Wang; Junlan Lv; Wei Shi; Victor Wei Zhang; Kei Murayama; Fang Fang

doi:10.1016/j.mito.2020.12.014

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.

Authors

Zhimei Liu¹, Masaru Shimura², Li Zhang³, Weihua Zhang¹, Jianing Wang⁴, Minako Ogawa-Tominaga², Junling Wang¹, Xiaohui Wang¹, Junlan Lv¹, Wei Shi⁵, Victor Wei Zhang⁶, Kei Murayama⁷, Fang Fang⁸

Affiliations

¹ Department of Neurology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China.
² Center for Medical Genetics and Department of Metabolism, Chiba Children's Hospital, Chiba 2660007, Japan.
³ Center for Bioinformatics and Computational Biology, and the Institute of Biomedical Sciences, School of Life Sciences, East China Normal University, Shanghai 200241, China.
⁴ College of Life Sciences, Nankai University, Tianjin 300071, China.
⁵ Department of Ophthalmology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China.
⁶ AmCare Genomics Lab, GuangZhou 510006, China.
⁷ Center for Medical Genetics and Department of Metabolism, Chiba Children's Hospital, Chiba 2660007, Japan. Electronic address: [email protected].
⁸ Department of Neurology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China. Electronic address: [email protected].

PMID: 33401012
DOI: 10.1016/j.mito.2020.12.014

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)