title: Enzymatic diagnostic test for Muscle-Eye-Brain type congenital muscular dystrophy using commercially available reagents.
abstract: OBJECTIVE
  Mutations disrupting the interaction of extra-cellular ligands and alpha-dystroglycan are responsible for an etiologically heterogeneous group of autosomal recessive congenital muscular dystrophies (CMD) that can have associated brain and eye abnormalities. The objective is to develop a diagnostic test for one of these CMDs, Muscle-Eye-Brain disease (MEB), due to mutations in the gene encoding Protein O-Mannosyl beta-1,2-N-acetylglucosaminyltransferase 1 (POMGnT1).
  
  
  METHODS
  POMGnT1 enzyme activity was determined in extracts of muscle biopsies from four MEB patients and various controls using commercially available reagents.
  
  
  RESULTS
  All four MEB muscle samples showed a highly significant decrease in POMGnT1 activity relative to controls.
  
  
  CONCLUSIONS
  The assay of POMGnT1 activity in MEB muscle provides a rapid and relatively simple diagnostic test for this disease. CMDs associated with brain malformations such as MEB, WWS and FCMD are heterogenous in clinical presentation and on radiologic examination, suggesting that POMGnT1 assays of muscle biopsies should be used as a screening procedure for MEB in all CMD patients associated with brain malformations.
authors.affiliation: Department of Structural Biology and Biochemistry, The Hospital for Sick Children, 555 University Avenue, Ont. M5G 1X8, Toronto, Canada.
authors.forename: Wenli
authors.initials: W
authors.lastname: Zhang
authors.forename: Jiri
authors.initials: J
authors.lastname: Vajsar
authors.forename: Pinjiang
authors.initials: P
authors.lastname: Cao
authors.forename: Galen
authors.initials: G
authors.lastname: Breningstall
authors.forename: Charlotta
authors.initials: C
authors.lastname: Diesen
authors.forename: William
authors.initials: W
authors.lastname: Dobyns
authors.forename: Ralph
authors.initials: R
authors.lastname: Herrmann
authors.forename: Anna-Elina
authors.initials: AE
authors.lastname: Lehesjoki
authors.forename: Alice
authors.initials: A
authors.lastname: Steinbrecher
authors.forename: Beril
authors.initials: B
authors.lastname: Talim
authors.forename: Tatsushi
authors.initials: T
authors.lastname: Toda
authors.forename: Haluk
authors.initials: H
authors.lastname: Topaloglu
authors.forename: Thomas
authors.initials: T
authors.lastname: Voit
authors.forename: Harry
authors.initials: H
authors.lastname: Schachter
mesh_terms: D001921:Brain / Q000002:abnormalities*; D003598:Cytoskeletal Proteins / Q000172:deficiency / Q000378:metabolism; D049030:Dystroglycans; D005124:Eye Abnormalities; D014453:Glucuronosyltransferase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000378:metabolism; D018482:Muscle, Skeletal / Q000002:abnormalities*; D009136:Muscular Dystrophies / Q000151:congenital / Q000175:diagnosis* / Q000201:enzymology; D009154:Mutation; D017351:N-Acetylglucosaminyltransferases / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism
chemical_list: D003598:Cytoskeletal Proteins; C483081:DAG1 protein, human; D008024:Ligands; D008562:Membrane Glycoproteins; D049030:Dystroglycans; D017351:N-Acetylglucosaminyltransferases; C443106:protein O-mannose beta-1,2-N-acetylglucosaminyltransferase; D014453:Glucuronosyltransferase