Skip Navigation


Human Molecular Genetics Advance Access originally published online on August 12, 2003
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
12/suppl_2/R259    most recent
ddg272v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Grewal, P. K.
Right arrow Articles by Hewitt, J. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Grewal, P. K.
Right arrow Articles by Hewitt, J. E.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Human Molecular Genetics, 2003, Vol. 12, Review Issue 2 R259-R264
DOI: 10.1093/hmg/ddg272
© 2003 Oxford University Press

Glycosylation defects: a new mechanism for muscular dystrophy?

Prabhjit K. Grewal{dagger} and Jane E. Hewitt*

Institute of Genetics, Queen's Medical Centre, University of Nottingham, Nottingham, UK

Received July 2, 2003; Accepted July 18, 2003

Recently, post-translational modification of proteins has been defined as a new area of focus for muscular dystrophy research by the identification of a group of disease genes that encode known or putative glycosylation enzymes. Walker–Warburg Syndrome (WWS) and muscle–eye–brain disease (MEB) are caused by mutations in two genes involved in O-mannosylation, POMT1 and POMGnT1, respectively. Fukuyama muscular dystrophy (FCMD) is due to mutations in fukutin, a putative phospholigand transferase. Congenital muscular dystrophy type 1C and limb girdle muscular dystrophy type 2I are allelic, both being due to mutations in the gene-encoding fukutin-related protein (FKRP). Finally, the causative gene in the myodystrophy (myd) mouse is a putative bifunctional glycosyltransferase (Large). WWS, MEB, FCMD and the myd mouse are also associated with neuronal migration abnormalities (often type II lissencephaly) and ocular or retinal defects. A deficiency in post-translational modification of {alpha}-dystroglycan is a common feature of all these muscular dystrophies and is thought to involve O-glycosylation pathways. This abnormally modified {alpha}-dystroglycan is deficient in binding to extracellular matrix ligands, including laminin and agrin. Selective deletion of dystroglycan in the central nervous system (CNS) produces brain abnormalities with striking similarities to WWS, MEB, FCMD and the myd mouse. Thus, impaired dystroglycan function is strongly implicated in these diseases. However, it is unlikely that these five glycosylation enzymes only have a role in glycosylation of {alpha}-dystroglycan and it is important that other protein targets are identified.

* To whom correspondence should be addressed at: Institute of Genetics, Queen's Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK. Tel: +44 1158493229; Fax: +44 1159709906; Email: jane.hewitt{at}nottingham.ac.uk

{dagger} Present address: Department of Cellular and Molecular Medicine, Howard Hughes Medical Institute, University of California San Diego, California 92093, USA.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Rheumatology (Oxford)Home page
A. Alavi and J. S. Axford
Sweet and sour: the impact of sugars on disease
Rheumatology, June 1, 2008; 47(6): 760 - 770.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
Y. P. Wairkar, L. G. Fradkin, J. N. Noordermeer, and A. DiAntonio
Synaptic Defects in a Drosophila Model of Congenital Muscular Dystrophy
J. Neurosci., April 2, 2008; 28(14): 3781 - 3789.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
R. B. Sher, C. Aoyama, K. A. Huebsch, S. Ji, J. Kerner, Y. Yang, W. N. Frankel, C. L. Hoppel, P. A. Wood, D. E. Vance, et al.
A Rostrocaudal Muscular Dystrophy Caused by a Defect in Choline Kinase Beta, the First Enzyme in Phosphatidylcholine Biosynthesis
J. Biol. Chem., February 24, 2006; 281(8): 4938 - 4948.
[Abstract] [Full Text] [PDF]

Home page
 J. Med. Genet.Home page
J van Reeuwijk, M Janssen, C van den Elzen, D Beltran-Valero de Bernabe, P Sabatelli, L Merlini, M Boon, H Scheffer, M Brockington, F Muntoni, et al.
POMT2 mutations cause {alpha}-dystroglycan hypoglycosylation and Walker-Warburg syndrome
J. Med. Genet., December 1, 2005; 42(12): 907 - 912.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
S. Kunz, J. M. Rojek, M. Kanagawa, C. F. Spiropoulou, R. Barresi, K. P. Campbell, and M. B. A. Oldstone
Posttranslational Modification of {alpha}-Dystroglycan, the Cellular Receptor for Arenaviruses, by the Glycosyltransferase LARGE Is Critical for Virus Binding
J. Virol., November 15, 2005; 79(22): 14282 - 14296.
[Abstract] [Full Text] [PDF]

Home page
 GlycobiologyHome page
P. K. Grewal, J. M. McLaughlan, C. J. Moore, C. A. Browning, and J. E. Hewitt
Characterization of the LARGE family of putative glycosyltransferases associated with dystroglycanopathies
Glycobiology, October 1, 2005; 15(10): 912 - 923.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
H. Huang, J. Sylvan, M. Jonas, R. Barresi, P. T. C. So, K. P. Campbell, and R. T. Lee
Cell stiffness and receptors: evidence for cytoskeletal subnetworks
Am J Physiol Cell Physiol, January 1, 2005; 288(1): C72 - C80.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
N. C. Connors, M. E. Adams, S. C. Froehner, and P. Kofuji
The Potassium Channel Kir4.1 Associates with the Dystrophin-Glycoprotein Complex via {alpha}-Syntrophin in Glia
J. Biol. Chem., July 2, 2004; 279(27): 28387 - 28392.
[Abstract] [Full Text] [PDF]

Home page
 NeurologyHome page
K. Sahashi, T. Ibi, K. Ohno, K. Sahashi, N. Nakao, and H. Kondo
Progressive myopathy with circulating autoantibody against giantin in the Golgi apparatus
Neurology, May 25, 2004; 62(10): 1891 - 1893.
[Abstract] [Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.