title: Adult-onset respiratory insufficiency, scoliosis, and distal joint hyperlaxity in patients with multiminicore disease due to novel Megf10 mutations.
abstract: Multiminicore disease is a congenital myopathy characterized pathologically by the presence of multiple minicore structures in the sarcoplasm. Mutations in the selenoprotein N1-encoding gene (SEPN1) and ryanodine receptor 1-encoding gene (RYR1) are responsible for half of the reported cases. Mutations in multiple epidermal growth factor-like domains 10-encoding gene (MEGF10) have been identified only recently in a few patients with antenatal to infantile-onset myopathy, with and without minicore pathology.
  
  
  
  We report 2 sisters with adult-onset respiratory insufficiency followed by development of limb weakness. Both had scoliosis, distal joint hyperlaxity, and high-arched feet.
  
  
  
  A biopsy of the right triceps muscle in 1 sister showed multiple minicore structures. She had electromyographic changes of myopathy with fibrillation potentials and myotonic discharges. Next generation sequencing identified novel compound heterozygous missense variants in MEGF10 c.230G>A (p.Arg77Gln) and c.1833T>G (p.Cys611Trp) in both sisters.
  
  
  
  MEGF10 mutations can cause myopathy with adult-onset respiratory insufficiency. Muscle Nerve, 2016 Muscle Nerve 53: 984-988, 2016.
authors.affiliation: Department of Neurology, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, Colorado, USA.|Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Teerin
authors.initials: T
authors.lastname: Liewluck
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Margherita
authors.initials: M
authors.lastname: Milone
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, NAB 2015, Houston, Texas, 77030, USA.
authors.forename: Xia
authors.initials: X
authors.lastname: Tian
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Engel
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Nathan P
authors.initials: NP
authors.lastname: Staff
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, NAB 2015, Houston, Texas, 77030, USA.
authors.forename: Lee-Jun
authors.initials: LJ
authors.lastname: Wong
mesh_terms: D000328:Adult; D005192:Family Health; D005260:Female; D006801:Humans; D007593:Joint Instability / Q000150:complications / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D020914:Myopathies, Structural, Congenital / Q000150:complications / Q000235:genetics*; D009886:Ophthalmoplegia / Q000150:complications / Q000235:genetics*; D012131:Respiratory Insufficiency / Q000150:complications / Q000235:genetics*; D019837:Ryanodine Receptor Calcium Release Channel / Q000172:deficiency* / Q000235:genetics; D012600:Scoliosis / Q000150:complications / Q000235:genetics*
chemical_list: C522055:MEGF10, human; D008565:Membrane Proteins; D019837:Ryanodine Receptor Calcium Release Channel
keywords: MEGF10; joint hyperlaxity; multiminicore disease; myopathy; myotonic discharges; respiratory insufficiency; scoliosis