HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) Correspondence: Submit a response Alert me when this article is cited Alert me when Correspondence are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mercuri, E. Articles by Muntoni, F. Search for Related Content PubMed PubMed Citation Articles by Mercuri, E. Articles by Muntoni, F.

Collagen VI involvement in Ullrich syndrome

A clinical, genetic, and immunohistochemical study

From the Dubowitz Neuromuscular Centre, Department of Paediatrics, Hammersmith Hospital Faculty of Medicine, Imperial College, London; and Department of Histopathology (Dr. Sewry), Robert Jones and Agnes Hunt Orthopaedic and District Hospital, Oswestry, United Kingdom.

Address correspondence and reprint requests to Dr. Eugenio Mercuri, Department of Paediatrics, Hammersmith Hospital, Du Cane Road, London W12 ONN, UK; e-mail: e.mercuri{at}ic.ac.uk

Background: Ullrich congenital muscular dystrophy (UCMD) is a form of merosin-positive congenital muscular dystrophy characterized by proximal contractures, distal laxity, rigidity of the spine, and respiratory complications. Recently, a deficiency of collagen VI on muscle and skin biopsy together with recessive mutations in the collagen 6A2 gene were reported in three families with UCMD. However, the clinical spectrum, frequency, and level of heterogeneity of this disorder are not known.

Subjects and Methods: The authors studied 15 patients (aged 3 to 23.6 years) with a clinical diagnosis of UCMD. Linkage analysis to the three collagen VI genes was performed in all informative families (n = 7), whereas immunohistochemical analysis of collagen VI expression in muscle was performed in the remaining cases.

Results: An immunocytochemical reduction of collagen VI was observed in six patients. Three of the six patients belonged to informative families, and haplotype analysis clearly suggested linkage to the COL6A1/2 locus in two cases and to the COL6A3 loci in the third case. In the remaining nine patients, primary collagen VI involvement was excluded based on either the linkage analysis (four families) or considered unlikely based on normal immunolabeling of collagen VI. Age and presentation at onset, the distribution and severity of weakness and contractures, and the frequency of nonambulant patients were similar in the patients with and without collagen VI involvement. Distal laxity, rigidity of the spine, scoliosis, failure to thrive, and early and severe respiratory impairment were found in all patients by the end of the first decade of life, irrespective of their maximum motor functional ability or their collagen status.

Conclusions: These results suggest that collagen VI involvement is relatively common in UCMD (40%); however, the role of this molecule was excluded in a number of cases, suggesting genetic heterogeneity of this condition.

This article has been cited by other articles:

				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]

				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]

				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]

				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]

				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]

				A K Lampe, D M Dunn, A C von Niederhausern, C Hamil, A Aoyagi, S H Laval, S K Marie, M-L Chu, K Swoboda, F Muntoni, et al. Automated genomic sequence analysis of the three collagen VI genes: applications to Ullrich congenital muscular dystrophy and Bethlem myopathy J. Med. Genet., February 1, 2005; 42(2): 108 - 120. [Abstract] [Full Text] [PDF]

				N. L. Baker, M. Morgelin, R. Peat, N. Goemans, K. N. North, J. F. Bateman, and S. R. Lamande Dominant collagen VI mutations are a common cause of Ullrich congenital muscular dystrophy Hum. Mol. Genet., January 15, 2005; 14(2): 279 - 293. [Abstract] [Full Text] [PDF]

				B Polla, G D'Antona, R Bottinelli, and C Reggiani Respiratory muscle fibres: specialisation and plasticity Thorax, September 1, 2004; 59(9): 808 - 817. [Abstract] [Full Text] [PDF]

				H. Ishikawa, K. Sugie, K. Murayama, A. Awaya, Y. Suzuki, S. Noguchi, Y. K. Hayashi, I. Nonaka, and I. Nishino Ullrich disease due to deficiency of collagen VI in the sarcolemma Neurology, February 24, 2004; 62(4): 620 - 623. [Abstract] [Full Text] [PDF]

				J. Kirschner and C. G. Bonnemann The Congenital and Limb-Girdle Muscular Dystrophies: Sharpening the Focus, Blurring the Boundaries Arch Neurol, February 1, 2004; 61(2): 189 - 199. [Abstract] [Full Text] [PDF]