title: Analysis of NCAM helps identify unusual phenotypes of hereditary inclusion-body myopathy.
abstract: BACKGROUND
  Hereditary inclusion-body myopathy or distal myopathy with rimmed vacuoles (h-IBM/DMRV) is due to mutations of the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) gene, which codes for an enzyme of the sialic acid biosynthetic pathway. By Western blot (WB) analysis, we have previously shown that in h-IBM/DMRV muscle, the neural cell adhesion molecule (NCAM) has increased electrophoretic mobility that reflects reduced sialylation of the protein.
  
  
  OBJECTIVE
  To identify patients with h-IBM/DMRV with atypical clinical or pathologic phenotype using NCAM analysis and the possible cellular mechanism associated with the overall abnormal sialylation of NCAM observed in this disorder.
  
  
  METHODS
  WB analysis of NCAM was performed on muscle biopsies of 84 patients with an uncharacterized muscle disorder who were divided in the following 2 groups: 1) 46 patients with a proximal muscle weakness in whom the main limb-girdle muscular dystrophy syndromes had been ruled out; and 2) 38 patients with a distal distribution of weakness in whom a neurogenic affection had been excluded. Patients in whom a reduced sialylation of NCAM was suspected were studied for the presence of GNE mutations.
  
  
  RESULTS
  In 3 patients, we found that NCAM had increased electrophoretic mobility, thus suggesting an abnormal sialylation of the protein. The genetic study demonstrated that they all carried pathogenic GNE mutations. Further studies demonstrated that hyposialylated NCAM, showing increased electrophoretic mobility on WB, is expressed by nonregenerating fibers in h-IBM/DMRV muscle.
  
  
  CONCLUSIONS
  WB analysis of NCAM may be instrumental in the identification of h-IBM/DMRV with atypical clinical or pathologic features.
authors.affiliation: Department of Neuroscience, Catholic University, Rome, Italy. a.broccolini@rm.unicatt.it
authors.forename: A
authors.initials: A
authors.lastname: Broccolini
authors.forename: T
authors.initials: T
authors.lastname: Gidaro
authors.forename: G
authors.initials: G
authors.lastname: Tasca
authors.forename: R
authors.initials: R
authors.lastname: Morosetti
authors.forename: C
authors.initials: C
authors.lastname: Rodolico
authors.forename: E
authors.initials: E
authors.lastname: Ricci
authors.forename: M
authors.initials: M
authors.lastname: Mirabella
mesh_terms: D000328:Adult; D049310:Distal Myopathies / Q000150:complications / Q000175:diagnosis* / Q000235:genetics*; D024202:Electrophoretic Mobility Shift Assay / Q000379:methods; D005260:Female; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D018908:Muscle Weakness / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000473:pathology; D009154:Mutation / Q000235:genetics; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism; D010641:Phenotype; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics*; D055815:Young Adult
chemical_list: D019006:Neural Cell Adhesion Molecules; D017853:Phosphotransferases (Alcohol Group Acceptor); C018765:N-acylmannosamine kinase