Megaconial Congenital Muscular Dystrophy Due to a Mutation in CHKB Gene: Two Cases in China

Yue Luo; Yingyin Liang; Li Feng; Jie Yang; Mansi Cai; Chao Wu; Zhicong Yan; Xiangxue Zhou; Xunhua Li; Huajing You; Dawei Liu; Bing Liao; Jinglang Wu; Huihua Yang; Xiuling Liang; Dingbang Chen

Megaconial Congenital Muscular Dystrophy Due to a Mutation in CHKB Gene: Two Cases in China

Yue Luo¹, Yingyin Liang¹, Li Feng¹, Jie Yang¹, Mansi Cai¹, Chao Wu¹, Zhicong Yan¹, Xiangxue Zhou¹, Xunhua Li¹, Huajing You¹, Dawei Liu¹, Bing Liao², Jinglang Wu³, Huihua Yang¹, Xiuling Liang¹, Dingbang Chen^1*

¹Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, The First Affiliated Hospital, Sun Yatsen University, Guangzhou, China

²Department of Pathology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou China,

³Electron Microscope Laboratory, Zhongshan Medical College, Sun Yat-Sen University, Guangzhou China

*Corresponding author: Dingbang Chen, Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China

Received Date: 29 January 2023

Accepted Date: 01 February 2023

Published Date: 03 February 2023

Citation: Luo Y, Liang Y, Feng L, Yang J, Cai M, et al (2023) Megaconial Congenital Muscular Dystrophy Due to a Mutation in CHKB Gene: Two Cases in China. Ann Case Report. 8: 1152. DOI:https://doi.org/10.29011/2574-7754.101152

Abstract

Megaconial congenital muscular dystrophy (MCMD) is a rare autosomal recessive disorder characterized by muscle weakness and intellectual disability attributed to CHKB mutations, which result in mitochondrial structural and functional abnormalities. We report two Chinese patients with Megaconial CMD. Patient 1 presented limb weakness and retardant intelligence from childhood. He was attacked by a cerebral embolism and was found to have dilated heart disease when he was 35 years old. A homozygous nonsense mutation (c.940C>T, p.Arg314Cys) was identified in CHKB gene. Light microscopic (LM) and electron microscopic (EM) examination on muscle fibres showed enlarged and peripherally displaced mitochondria. Patient 2 was a 15-month-old boy when he visited. He was found to be floppy at birth. He has limb weakness and show delay motor development as he grows. Muscle MR showed sparse muscle and fatty deposits in muscle in bilateral upper arms, bilateral thighs. A muscle biopsy showed basophilic particles gathered around muscle fibres. Histochemical staining for oxidative enzymes (SDH and COX) showed enhanced staining of large particles. Electron microscopy showed the fibres presented mitochondria enlarged in length and diameter. A c.598del (p.Gln200Argfs*11) homozygous mutation in CHKB gene was found. His parents are heterozygous carrier at this locus. This is the first report of Han Chinese patients with Megaconial CMD in China Mainland, and a new mutation was found.

Keywords: Megaconial Congenital Muscular Dystrophy; Choline Kinase Beta; Enlarged Mitochondria

Abbreviations: MDCMC: Muscular Dystrophy, Congenital, Megaconial Type; CHKB: Choline Kinase Beta; LM: Light Microscopic; EM: Electron Microscopic; CK: Creatine Kinase; HGMD: The Human Gene Mutation Database; MELAS: Mitochondrial Encephalomyopathy, Lactic Acidosis, and StrokeLike Episodes; ESP: Exome Sequencing Project; NADH-TR: Nicotinamide Adenine Dinucleotide Tetrazolium Reductase; ATP: Adenosine Triphosphate; SDH: Succinate Dehydrogenase; COX: Cytochrome Oxidase