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Enzymatic diagnostic test for Muscle-Eye-Brain type congenital muscular dystrophy using commercially available
Wenli Zhang1, Jiri Vajsar, Pinjiang Cao
1Department of Structural Biology and Biochemistry, The Hospital for Sick Children, 555 University Avenue, Ont. M5G 1X8, Toronto, Canada.
Objectives:
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).
Design And 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.
Insights
A diagnostic test for Muscle-Eye-Brain disease (MEB) was developed by measuring Protein O-Mannosyl beta-1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) enzyme activity in muscle biopsies. MEB patients showed significantly decreased POMGnT1 activity.
Area of Science:
- Biochemistry
- Genetics
- Neurology
Background:
- Congenital muscular dystrophies (CMDs) encompass a group of inherited muscle disorders.
- Mutations affecting the dystroglycan complex can lead to CMDs with neurological and ocular manifestations.
- Muscle-Eye-Brain disease (MEB) is an autosomal recessive CMD linked to mutations in the POMGnT1 gene.
Purpose of the Study:
- To develop a diagnostic test for Muscle-Eye-Brain disease (MEB).
- To investigate the utility of measuring Protein O-Mannosyl beta-1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) enzyme activity for MEB diagnosis.
Main Methods:
- Muscle biopsies were obtained from four MEB patients and control individuals.
- POMGnT1 enzyme activity was quantified using commercially available reagents.
Main Results:
- All four MEB patient muscle samples exhibited significantly reduced POMGnT1 enzyme activity compared to controls.
- This decrease in activity suggests a functional deficiency in POMGnT1 in MEB patients.
Conclusions:
- Assessing POMGnT1 activity in muscle biopsies offers a rapid and straightforward diagnostic method for MEB.
- Given the heterogeneity of CMDs with brain malformations, POMGnT1 assays should be considered for screening MEB in affected patients.