title: Clinical features of congenital myasthenic syndrome due to mutations in DPAGT1.
abstract: BACKGROUND
  A newly defined congenital myasthenic syndrome (CMS) caused by DPAGT1 mutations has recently been reported. While many other CMS-associated proteins have discrete roles localised to the neuromuscular junction, DPAGT1 is ubiquitously expressed, modifying many proteins, and as such is an unexpected cause of isolated neuromuscular involvement.
  
  
  METHODS
  We present detailed clinical characteristics of five patients with CMS caused by DPAGT1 mutations.
  
  
  RESULTS
  Patients have prominent limb girdle weakness and minimal craniobulbar symptoms. Tubular aggregates on muscle biopsy are characteristic but may not be apparent on early biopsies. Typical myasthenic features such as pyridostigmine and 3, 4- diaminopyridine responsiveness, and decrement on repetitive nerve stimulation are present.
  
  
  CONCLUSIONS
  These patients mimic myopathic disorders and are likely to be under-diagnosed. The descriptions here should facilitate recognition of this disorder. In particular minimal craniobulbar involvement and tubular aggregates on muscle biopsy help to distinguish DPAGT1 CMS from the majority of other forms of CMS. Patients with DPAGT1 CMS share similar clinical features with patients who have CMS caused by mutations in GFPT1, another recently identified CMS subtype.
authors: Neurosciences Group, Nuffield Department of Clinical Neurosciences, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK. sarah.finlayson@clneuro.ox.ac.uk
authors: Sarah
authors: S
authors: Finlayson
authors: Jacqueline
authors: J
authors: Palace
authors: Katsiaryna
authors: K
authors: Belaya
authors: Timothy J
authors: TJ
authors: Walls
authors: Fiona
authors: F
authors: Norwood
authors: Georgina
authors: G
authors: Burke
authors: Janice L
authors: JL
authors: Holton
authors: Samuel I
authors: SI
authors: Pascual-Pascual
authors: Judith
authors: J
authors: Cossins
authors: David
authors: D
authors: Beeson
mesh_terms: D015761:4-Aminopyridine / Q000031:analogs & derivatives / Q000627:therapeutic use; D058666:Adrenergic beta-2 Receptor Agonists; D000328:Adult; D017668:Age of Onset; D000420:Albuterol / Q000627:therapeutic use; D000077770:Amifampridine; D001706:Biopsy; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D059472:Exome; D005260:Female; D005820:Genetic Testing; D006031:Glycosylation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009046:Motor Neurons / Q000502:physiology; D018482:Muscle, Skeletal / Q000294:innervation / Q000473:pathology; D020294:Myasthenic Syndromes, Congenital / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics*; D009460:Neurologic Examination; D009469:Neuromuscular Junction / Q000502:physiology; D010641:Phenotype; D026902:Potassium Channel Blockers / Q000627:therapeutic use; D011729:Pyridostigmine Bromide / Q000627:therapeutic use
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D002800:Cholinesterase Inhibitors; D026902:Potassium Channel Blockers; D015761:4-Aminopyridine; D017351:N-Acetylglucosaminyltransferases; C047835:dolichyl-phosphate alpha-N-acetylglucosaminyltransferase; D011729:Pyridostigmine Bromide; D000420:Albuterol; D000077770:Amifampridine
keywords: Genetics; Molecular Biology; Myasthenia; Myopathy; Neuropathology, Muscle