Journal article
A comparative study of α-dystroglycan glycosylation in dystroglycanopathies suggests that the hypoglycosylation of α-dystroglycan does not consistently correlate with clinical severity
Brain pathology (Zurich, Switzerland), Vol.19(4), pp.596-611
10/2009
DOI: 10.1111/j.1750-3639.2008.00198.x
PMCID: PMC2860390
PMID: 18691338
Abstract
Hypoglycosylation of α-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 6 genes have been identified in a proportion of patients.
POMT1, POMT2
and
POMGnT1
encode for glycosyltransferases involved in the mannosylation of α-dystroglycan but the function of
fukutin, FKRP
and
LARG
E is less clear. The pathological hallmark is reduced immunolabelling of skeletal muscle with antibodies recognising glycosylated epitopes on α-dystroglycan. If the common pathway of these conditions is the hypoglycosyation of α-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 α-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 α-dystroglycan. These data indicate that it is not always possible to correlate clinical course and α-dystroglycan labelling and suggest that there might be differences in α-dystroglycan processing in these disorders.
Details
- Title: Subtitle
- A comparative study of α-dystroglycan glycosylation in dystroglycanopathies suggests that the hypoglycosylation of α-dystroglycan does not consistently correlate with clinical severity
- Creators
- Cecilia Jimenez-Mallebrera - Dubowitz Neuromuscular Centre, Institute of Child Health and Great Ormond Street Hospital for Children, UCL, London, United KingdomSilvia Torelli - Dubowitz Neuromuscular Centre, Institute of Child Health and Great Ormond Street Hospital for Children, UCL, London, United KingdomLucy Feng - Dubowitz Neuromuscular Centre, Institute of Child Health and Great Ormond Street Hospital for Children, UCL, London, United KingdomJihee Kim - Dubowitz Neuromuscular Centre, Institute of Child Health and Great Ormond Street Hospital for Children, UCL, London, United KingdomCaroline Godfrey - Dubowitz Neuromuscular Centre, Institute of Child Health and Great Ormond Street Hospital for Children, UCL, London, United KingdomEmma Clement - Dubowitz Neuromuscular Centre, Institute of Child Health and Great Ormond Street Hospital for Children, UCL, London, United KingdomRachael Mein - DNA Laboratory, Genetics Centre, Guy’s Hospital, London, United KingdomStephen Abbs - DNA Laboratory, Genetics Centre, Guy’s Hospital, London, United KingdomSusan C Brown - Dubowitz Neuromuscular Centre, Institute of Child Health and Great Ormond Street Hospital for Children, UCL, London, United KingdomKevin P Campbell - Howard Hughes Medical Institute, Department of Molecular Physiology and Biophysics, Internal Medicine and Neurology, University of Iowa Carver College of Medicine, Iowa City, Iowa, USAS Kroger - Physiological Institute, Ludwig-Maximilians-University, Munich, GermanyBeril Talim - Department of Paediatric Pathology, Hacettepe Children’s Hospital, Ankara, TurkeyHaluk Topaloglu - Child Neurology Unit, Department of Pediatrics, Hacettepe University, Ankara, TurkeyRos Quinlivan - Wolfson Centre for Inherited Neuromuscular Diseases, Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry, United KingdomHelen Roper - Department of Paediatrics, Birmingham Heartlands Hospital, Birmingham, UKAnne M Childs - Department of Paediatric Neurosciences, Leeds General Infirmary, Leeds, UKMaria Kinali - Dubowitz Neuromuscular Centre, Institute of Child Health and Great Ormond Street Hospital for Children, UCL, London, United KingdomCaroline A Sewry - Dubowitz Neuromuscular Centre, Institute of Child Health and Great Ormond Street Hospital for Children, UCL, London, United KingdomFrancesco Muntoni - Dubowitz Neuromuscular Centre, Institute of Child Health and Great Ormond Street Hospital for Children, UCL, London, United Kingdom
- Resource Type
- Journal article
- Publication Details
- Brain pathology (Zurich, Switzerland), Vol.19(4), pp.596-611
- DOI
- 10.1111/j.1750-3639.2008.00198.x
- PMID
- 18691338
- PMCID
- PMC2860390
- ISSN
- 1015-6305
- eISSN
- 1750-3639
- Language
- English
- Date published
- 10/2009
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute
- Record Identifier
- 9984020711102771
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