title: Diagnosis and etiology of congenital muscular dystrophy.
abstract: OBJECTIVE
  We aimed to determine the frequency of all known forms of congenital muscular dystrophy (CMD) in a large Australasian cohort.
  
  
  METHODS
  We screened 101 patients with CMD with a combination of immunofluorescence, Western blotting, and DNA sequencing to identify disease-associated abnormalities in glycosylated alpha-dystroglycan, collagen VI, laminin alpha2, alpha7-integrin, and selenoprotein.
  
  
  RESULTS
  A total of 45% of the CMD cohort were assigned to an immunofluorescent subgroup based on their abnormal staining pattern. Abnormal staining for glycosylated alpha-dystroglycan was present in 25% of patients, and approximately half of these had reduced glycosylated alpha-dystroglycan by Western blot. Sequencing of the FKRP, fukutin, POMGnT1, and POMT1 genes in all patients with abnormal alpha-dystroglycan immunofluorescence identified mutations in one patient for each of these genes and two patients had mutations in POMT2. Twelve percent of patients had abnormalities in collagen VI immunofluorescence, and we identified disease-causing COL6 mutations in eight of nine patients in whom the genes were sequenced. Laminin alpha2 deficiency accounted for only 8% of CMD. alpha7-Integrin staining was absent in 12 of 45 patients studied, and ITGA7 gene mutations were excluded in all of these patients.
  
  
  CONCLUSIONS
  We define the distribution of different forms of congenital muscular dystrophy in a large cohort of mixed ethnicity and demonstrate the utility and limitations of current diagnostic techniques.
authors.affiliation: Institute for Neuromuscular Research, The Children's Hospital at Westmead, Sydney, NSW, Australia.
authors.forename: R A
authors.initials: RA
authors.lastname: Peat
authors.forename: J M
authors.initials: JM
authors.lastname: Smith
authors.forename: A G
authors.initials: AG
authors.lastname: Compton
authors.forename: N L
authors.initials: NL
authors.lastname: Baker
authors.forename: R A
authors.initials: RA
authors.lastname: Pace
authors.forename: D J
authors.initials: DJ
authors.lastname: Burkin
authors.forename: S J
authors.initials: SJ
authors.lastname: Kaufman
authors.forename: S R
authors.initials: SR
authors.lastname: Lamandé
authors.forename: K N
authors.initials: KN
authors.lastname: North
mesh_terms: D044362:Australasia / Q000208:ethnology; D015153:Blotting, Western; D002675:Child, Preschool; D015331:Cohort Studies; D024142:Collagen Type VI / Q000235:genetics; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D049030:Dystroglycans / Q000172:deficiency / Q000235:genetics; D005006:Ethnicity / Q000235:genetics; D005260:Female; D005455:Fluorescent Antibody Technique; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008364:Mannosyltransferases / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009136:Muscular Dystrophies / Q000151:congenital* / Q000175:diagnosis / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics
chemical_list: D024142:Collagen Type VI; C113587:FKTN protein, human; D008565:Membrane Proteins; D009124:Muscle Proteins; D049030:Dystroglycans; D008364:Mannosyltransferases; D017351:N-Acetylglucosaminyltransferases; C443106:protein O-mannose beta-1,2-N-acetylglucosaminyltransferase; C082696:protein O-mannosyltransferase