Enzymatic diagnostic test for Muscle-Eye-Brain type congenital muscular dystrophy using commercially available reagents.
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.
Zhang
Wenli
W
Department of Structural Biology and Biochemistry, The Hospital for Sick Children, 555 University Avenue, Ont. M5G 1X8, Toronto, Canada.
Vajsar
Jiri
J
Cao
Pinjiang
P
Breningstall
Galen
G
Diesen
Charlotta
C
Dobyns
William
W
Herrmann
Ralph
R
Lehesjoki
Anna-Elina
AE
Steinbrecher
Alice
A
Talim
Beril
B
Toda
Tatsushi
T
Topaloglu
Haluk
H
Voit
Thomas
T
Schachter
Harry
H
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
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