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A Comparative Study of α-Dystroglycan Glycosylation in Dystroglycanopathies Suggests that the Hypoglycosylation of α-Dystroglycan Does Not Consistently Correlate with Clinical Severity
- Source :
- Brain Pathology. 19:596-611
- Publication Year :
- 2009
- Publisher :
- Wiley, 2009.
-
Abstract
- Hypoglycosylation of alpha-dystroglycan underpins a subgroup of muscular dystrophies ranging from congenital onset of weakness, severe brain malformations and death in the perinatal period to mild weakness in adulthood without brain involvement. Mutations in six genes have been identified in a proportion of patients. POMT1, POMT2 and POMGnT1 encode for glycosyltransferases involved in the mannosylation of alpha-dystroglycan but the function of fukutin, FKRP and LARGE is less clear. The pathological hallmark is reduced immunolabeling of skeletal muscle with antibodies recognizing glycosylated epitopes on alpha-dystroglycan. If the common pathway of these conditions is the hypoglycosyation of alpha-dystroglycan, one would expect a correlation between clinical severity and the extent of hypoglycosylation. By studying 24 patients with mutations in these genes, we found a good correlation between reduced alpha-dystroglycan staining and clinical course in patients with mutations in POMT1, POMT2 and POMGnT1. However, this was not always the case in patients with defects in fukutin and FKRP, as we identified patients with mild limb-girdle phenotypes without brain involvement with profound depletion of alpha-dystroglycan. These data indicate that it is not always possible to correlate clinical course and alpha-dystroglycan labeling and suggest that there might be differences in alpha-dystroglycan processing in these disorders.
- Subjects :
- musculoskeletal diseases
congenital, hereditary, and neonatal diseases and abnormalities
Pathology
medicine.medical_specialty
Glycosylation
Adolescent
Genotype
Biopsy
DNA Mutational Analysis
Biology
Severity of Illness Index
Muscular Dystrophies
Article
Pathology and Forensic Medicine
Dystroglycans
Laminin
medicine
Humans
Child
Muscle, Skeletal
Walker–Warburg syndrome
Fukutin-related protein
Staining and Labeling
General Neuroscience
fungi
Infant
medicine.disease
Immunohistochemistry
Fukutin
Phenotype
Child, Preschool
Mannosylation
Mutation
Congenital muscular dystrophy
biology.protein
Neurosciences & Neurology
Neurology (clinical)
Limb-girdle muscular dystrophy
Subjects
Details
- ISSN :
- 17503639 and 10156305
- Volume :
- 19
- Database :
- OpenAIRE
- Journal :
- Brain Pathology
- Accession number :
- edsair.doi.dedup.....76e84c1af9482f4569e72946cb1a6e1e
- Full Text :
- https://doi.org/10.1111/j.1750-3639.2008.00198.x