title: Proximal myopathy with focal depletion of mitochondria and megaconial congenital muscular dystrophy are allelic conditions caused by mutations in CHKB.
abstract: We recently evaluated two of the original three patients (siblings) diagnosed with Proximal Myopathy with Focal Depletion of Mitochondria. The condition was named for the distinctive pattern of enlarged mitochondria around the periphery of muscle fibres with a complete absence in the middle. These siblings, aged 37 and 40, are cognitively normal with mild non-progressive muscle weakness and a susceptibility to rhabdomyolysis. Both were shown to be compound heterozygotes for novel mutations (c.263C>T + c.950T>A) in CHKB, the gene currently associated with Megaconial Congenital Muscular Dystrophy. Individuals with this condition have early-onset muscle weakness and profound intellectual disability but share the same unique pattern on muscle biopsy as was noted in Proximal Myopathy with Focal Depletion of Mitochondria; focal depletion of mitochondria was surrounded by abnormally large "megaconial" mitochondria. Thus the phenotypic spectrum of CHKB mutations ranges from a congenital muscular dystrophy with intellectual disability to a later-onset non-progressive muscular weakness with normal cognition.
authors.affiliation: Department of Pediatrics, McMaster University Medical Centre, 1200 Main Street West, Hamilton, Ontario L8N 3Z5, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Brady
authors.affiliation: Children's National Medical Center, Research Center for Genetic Medicine, 111 Michigan Ave, Washington D.C. 20010, USA.
authors.forename: M
authors.initials: M
authors.lastname: Giri
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Provias
authors.affiliation: Children's National Medical Center, Research Center for Genetic Medicine, 111 Michigan Ave, Washington D.C. 20010, USA.
authors.forename: E
authors.initials: E
authors.lastname: Hoffman
authors.affiliation: Department of Pediatrics, McMaster University Medical Centre, 1200 Main Street West, Hamilton, Ontario L8N 3Z5, Canada. Electronic address: tarnopol@mcmaster.ca.
authors.forename: M
authors.initials: M
authors.lastname: Tarnopolsky
mesh_terms: D000328:Adult; D002797:Choline Kinase / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D028361:Mitochondrial Diseases / Q000235:genetics* / Q000503:physiopathology*; D009135:Muscular Diseases / Q000235:genetics* / Q000503:physiopathology*; D009136:Muscular Dystrophies / Q000235:genetics* / Q000503:physiopathology*; D010641:Phenotype; D035781:Siblings
chemical_list: C542592:CHKB protein, human; D002797:Choline Kinase
keywords: CHKB; Megaconial muscular dystrophy; Mitochondrial depletion; Myalgia; Oligomitochondria; Rhabdomyolysis