title: Novel GNE compound heterozygous mutations in a GNE myopathy patient.
abstract: BACKGROUND
  Molecular studies have revealed that some patients with myopathies with rimmed vacuoles have pathogenic mutations in the UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (GNE) and Z-band alternatively spliced PDZ motif-containing protein (ZASP) genes.
  
  
  METHODS
  We investigated a patient with distal myopathy with rimmed vacuoles by muscle biopsy and sequenced 6 candidate genes.
  
  
  RESULTS
  The patient carried GNE compound heterozygous missense mutations (p.V421A and p.N635K) and a ZASP variant (p.D673N). This patient also presented with distal weakness sparing the quadriceps muscles and had atypical results for Z-band-associated protein immunostaining. This finding indicates that the GNE mutations are pathogenic, and the diagnosis is compatible with GNE myopathy.
  
  
  CONCLUSIONS
  By combining pathological studies and candidate gene screening, we identified a patient with GNE myopathy due to novel GNE compound heterozygous mutations.
authors.affiliation: Department of Neurology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo, 060-8638, Japan.
authors.forename: Huaying
authors.initials: H
authors.lastname: Cai
authors.forename: Ichiro
authors.initials: I
authors.lastname: Yabe
authors.forename: Shinichi
authors.initials: S
authors.lastname: Shirai
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nishimura
authors.forename: Makoto
authors.initials: M
authors.lastname: Hirotani
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kano
authors.forename: Hideki
authors.initials: H
authors.lastname: Houzen
authors.forename: Kazuto
authors.initials: K
authors.lastname: Yoshida
authors.forename: Hidenao
authors.initials: H
authors.lastname: Sasaki
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D005260:Female; D006580:Genetic Carrier Screening; D006801:Humans; D060588:LIM Domain Proteins / Q000235:genetics*; D008875:Middle Aged; D009097:Multienzyme Complexes / Q000235:genetics*; D018482:Muscle, Skeletal / Q000737:chemistry / Q000473:pathology*; D009135:Muscular Diseases / Q000235:genetics* / Q000473:pathology; D020125:Mutation, Missense / Q000235:genetics; D014617:Vacuoles / Q000235:genetics / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C120696:LDB3 protein, human; D060588:LIM Domain Proteins; D009097:Multienzyme Complexes; C482901:UDP-N-acetylglucosamine 2-epimerase - N-acetylmannosamine kinase
keywords: GNE myopathy; UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (GNE); Z-band alternatively spliced PDZ motif-containing protein (ZASP); distal myopathy with rimmed vacuoles; myofibrillar myopathy