Skip Navigation


Human Molecular Genetics Advance Access originally published online on November 24, 2004
Human Molecular Genetics 2005 14(2):279-293; doi:10.1093/hmg/ddi025
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
14/2/279    most recent
ddi025v1
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 ISI Web of Science
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 arrow Search for citing articles in:
ISI Web of Science (41)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Baker, N. L.
Right arrow Articles by Lamandé, S. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Baker, N. L.
Right arrow Articles by Lamandé, S. R.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Human Molecular Genetics, Vol. 14, No. 2 © Oxford University Press 2005; all rights reserved

Dominant collagen VI mutations are a common cause of Ullrich congenital muscular dystrophy

Naomi L. Baker1, Matthias Mörgelin2, Rachel Peat3, Nathalie Goemans4, Kathryn N. North3, John F. Bateman1 and Shireen R. Lamandé1,*

1Cell and Matrix Biology, Murdoch Childrens Research Institute and Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Parkville, Victoria 3052, Australia, 2Department of Cell and Molecular Biology, Section of Molecular Pathogenesis, Lund University, 221 84 Lund, Sweden, 3Institute for Neuromuscular Research, The Children's Hospital at Westmead and Department of Paediatrics and Child Health, University of Sydney, Australia and 4Department of Paediatric Neurology, University Hospital, Leuven, Belgium

* To whom correspondence should be addressed. Tel: +61 393456650; Fax: +61 393457997; Email: shireen.lamande{at}mcri.edu.au

Received June 1, 2004; Accepted November 11, 2004

Mutations in the three collagen VI genes COL6A1, COL6A2 and COL6A3 cause Bethlem myopathy and Ullrich congenital muscular dystrophy (UCMD). UCMD, a severe disorder characterized by congenital muscle weakness, proximal joint contractures and marked distal joint hyperextensibility, has been considered a recessive condition, and homozygous or compound heterozygous mutations have been defined in COL6A2 and COL6A3. In contrast, the milder disorder Bethlem myopathy shows clear dominant inheritance and is caused by heterozygous mutations in COL6A1, COL6A2 and COL6A3. This model, where dominant mutations cause mild Bethlem myopathy and recessive mutations cause severe UCMD was recently challenged when a patient with UCMD was shown to have a heterozygous in-frame deletion in COL6A1. We have studied five patients with a clinical diagnosis of UCMD. Three patients had heterozygous in-frame deletions in the N-terminal region of the triple helical domain, one in the {alpha}1(VI) chain, one in {alpha}2(VI) and one in {alpha}3(VI). Collagen VI protein biosynthesis and assembly studies showed that these mutations act in a dominant negative fashion and result in severe collagen VI matrix deficiencies. One patient had recessive amino acid changes in the C2 subdomain of {alpha}2(VI), which prevented collagen VI assembly. No collagen VI mutations were found in the fifth patient. These data demonstrate that rather than being a rare cause of UCMD, dominant mutations are common in UCMD, now accounting for four of the 14 published cases. Mutation detection in this disorder remains critical for accurate genetic counseling of patients and their families.


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
 NeurologyHome page
L. Merlini, E. Martoni, P. Grumati, P. Sabatelli, S. Squarzoni, A. Urciuolo, A. Ferlini, F. Gualandi, and P. Bonaldo
Autosomal recessive myosclerosis myopathy is a collagen VI disorder
Neurology, October 14, 2008; 71(16): 1245 - 1253.
[Abstract] [Full Text] [PDF]

Home page
 NeurologyHome page
R. A. Peat, J. M. Smith, A. G. Compton, N. L. Baker, R. A. Pace, D. J. Burkin, S. J. Kaufman, S. R. Lamande, and K. N. North
Diagnosis and etiology of congenital muscular dystrophy
Neurology, July 29, 2008; 71(5): 312 - 321.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. Fitzgerald, C. Rich, F. H. Zhou, and U. Hansen
Three Novel Collagen VI Chains, {alpha}4(VI), {alpha}5(VI), and {alpha}6(VI)
J. Biol. Chem., July 18, 2008; 283(29): 20170 - 20180.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. K. Gara, P. Grumati, A. Urciuolo, P. Bonaldo, B. Kobbe, M. Koch, M. Paulsson, and R. Wagener
Three Novel Collagen VI Chains with High Homology to the {alpha}3 Chain
J. Biol. Chem., April 18, 2008; 283(16): 10658 - 10670.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
L. Merlini, A. Angelin, T. Tiepolo, P. Braghetta, P. Sabatelli, A. Zamparelli, A. Ferlini, N. M. Maraldi, P. Bonaldo, and P. Bernardi
Cyclosporin A corrects mitochondrial dysfunction and muscle apoptosis in patients with collagen VI myopathies
PNAS, April 1, 2008; 105(13): 5225 - 5229.
[Abstract] [Full Text] [PDF]

Home page
 NeurologyHome page
D. Hicks, A. K. Lampe, R. Barresi, R. Charlton, C. Fiorillo, C. G. Bonnemann, J. Hudson, R. Sutton, H. Lochmuller, V. Straub, et al.
A refined diagnostic algorithm for Bethlem myopathy
Neurology, April 1, 2008; 70(14): 1192 - 1199.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
L. Sipila, H. Ruotsalainen, R. Sormunen, N. L. Baker, S. R. Lamande, M. Vapola, C. Wang, Y. Sado, A. Aszodi, and R. Myllyla
Secretion and Assembly of Type IV and VI Collagens Depend on Glycosylation of Hydroxylysines
J. Biol. Chem., November 16, 2007; 282(46): 33381 - 33388.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
D. K. Spangenberg and G. L. Waring
A Mutant dec-1 Transgene Induces Dominant Female Sterility in Drosophila melanogaster
Genetics, November 1, 2007; 177(3): 1595 - 1608.
[Abstract] [Full Text] [PDF]

Home page
 NeurologyHome page
M. Okada, G. Kawahara, S. Noguchi, K. Sugie, K. Murayama, I. Nonaka, Y. K. Hayashi, and I. Nishino
Primary collagen VI deficiency is the second most common congenital muscular dystrophy in Japan
Neurology, September 4, 2007; 69(10): 1035 - 1042.
[Abstract] [Full Text] [PDF]

Home page
 NeurologyHome page
G. Kawahara, M. Okada, N. Morone, C. A. Ibarra, I. Nonaka, S. Noguchi, Y. K. Hayashi, and I. Nishino
Reduced cell anchorage may cause sarcolemma-specific collagen VI deficiency in Ullrich disease
Neurology, September 4, 2007; 69(10): 1043 - 1049.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
K. E. Kadler, C. Baldock, J. Bella, and R. P. Boot-Handford
Collagens at a glance
J. Cell Sci., June 15, 2007; 120(12): 1955 - 1958.
[Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
A. Angelin, T. Tiepolo, P. Sabatelli, P. Grumati, N. Bergamin, C. Golfieri, E. Mattioli, F. Gualandi, A. Ferlini, L. Merlini, et al.
Mitochondrial dysfunction in the pathogenesis of Ullrich congenital muscular dystrophy and prospective therapy with cyclosporins
PNAS, January 16, 2007; 104(3): 991 - 996.
[Abstract] [Full Text] [PDF]

Home page
 BrainHome page
M. Tetreault, A. Duquette, I. Thiffault, C. Bherer, J. Jarry, L. Loisel, B. Banwell, G. D'Anjou, J. Mathieu, Y. Robitaille, et al.
A new form of congenital muscular dystrophy with joint hyperlaxity maps to 3p23-21
Brain, August 1, 2006; 129(8): 2077 - 2084.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. R. Lamande, M. Morgelin, N. E. Adams, C. Selan, and J. M. Allen
The C5 Domain of the Collagen VI {alpha}3(VI) Chain Is Critical for Extracellular Microfibril Formation and Is Present in the Extracellular Matrix of Cultured Cells
J. Biol. Chem., June 16, 2006; 281(24): 16607 - 16614.
[Abstract] [Full Text] [PDF]

Home page
 Rheumatology (Oxford)Home page
F. Malfait, A. J. Hakim, A. De Paepe, and R. Grahame
The genetic basis of the joint hypermobility syndromes
Rheumatology, May 1, 2006; 45(5): 502 - 507.
[Full Text] [PDF]

Home page
 J. Med. Genet.Home page
A K Lampe and K M D Bushby
Collagen VI related muscle disorders
J. Med. Genet., September 1, 2005; 42(9): 673 - 685.
[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.