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Novel collagen VI mutations identified in Chinese patients with Ullrich congenital muscular dystrophy

World Journal of Pediatrics volume 10, pages 126–132 (2014)Cite this article

Abstract

Background

We determined the clinical and molecular genetic characteristics of 8 Chinese patients with Ullrich congenital muscular dystrophy (UCMD).

Methods

Clinical data of probands were collected and muscle biopsies of patients were analyzed. Exons of COL6A1, COL6A2 and COL6A3 were analyzed by direct sequencing. Mutations in COL6A1, COL6A2 and COL6A3 were identified in 8 patients.

Results

Among these mutations, 5 were novel [three in the triple helical domain (THD) and 2 in the second C-terminal (C2) domain]. We also identified five known missense or in-frame deletion mutations in THD and C domains. Immunohistochemical studies on muscle biopsies from patients showed reduced level of collagen VI at the muscle basement membrane and mis-localization of the protein in interstitial and perivascular regions.

Conclusions

The novel mutations we identified underscore the importance of THD and C2 domains in the assembly and function of collagen VI, thereby providing useful information for the genetic counseling of UCMD patients.

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References

  1. Ullrich O. Kongenitale, atonisch-sklerotische Muskeldystrophie, ein weiterer Typus der heredodegenerativen Erkrankungen des neuromuskulären Systems. Zeitschrift für die gesamte Neurologie und Psychiatrie 1930;126:171–201.

    Article  Google Scholar 

  2. Mercuri E, Yuva Y, Brown SC, Brockington M, Kinali M, Jungbluth H, et al. Collagen VI involvement in Ullrich syndrome: a clinical, genetic, and immunohistochemical study. Neurology 2002;58:1354–1359.

    CAS  PubMed  Article  Google Scholar 

  3. Lampe AK, Bushby KM. Collagen VI related muscle disorders. J Med Genet 2005;42:673–685.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  4. Muntoni F, Bertini E, Bönnemann C, Brockington M, Brown S, Bushby K, et al. 98th ENMC International Workshop on Congenital Muscular Dystrophy (CMD), 7th Workshop of the International Consortium on CMD, 2nd Workshop of the MYO CLUSTER project GENRE. 26–28th October, 2001, Naarden, The Netherlands. Neuromuscul Disord 2002;12:889–896.

    CAS  Google Scholar 

  5. Muntoni F, Voit T. The congenital muscular dystrophies in 2004: a century of exciting progress. Neuromuscul Disord 2004;14:635–649.

    PubMed  Article  Google Scholar 

  6. Briñas L, Richard P, Quijano-Roy S, Gartioux C, Ledeuil C, Lacène E, et al. Early onset collagen VI myopathies: Genetic and clinical correlations. Ann Neurol 2010;68:511–520.

    PubMed  Article  Google Scholar 

  7. Allamand V, Merlini L, Bushby K; Consortium for Collagen VI-Related Myopathies. 166th ENMC International Workshop on Collagen type VI-Related Myopathies, 22–24 May 2009, Naarden, the Netherlands. Neuromuscul Disord 2010;20:346–354.

    PubMed  Article  Google Scholar 

  8. Okada M, Kawahara G, Noguchi S, Sugie K, Murayama K, Nonaka I, et al. Primary collagen VI deficiency is the second most common congenital muscular dystrophy in Japan. Neurology 2007;69:1035–1042.

    CAS  PubMed  Article  Google Scholar 

  9. Pace RA, Peat RA, Baker NL, Zamurs L, Mörgelin M, Irving M, et al. Collagen VI glycine mutations: perturbed assembly and a spectrum of clinical severity. Ann Neurol 2008;64:294–303.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  10. Schessl J, Zou Y, Bönnemann CG. Congenital Muscular Dystrophies and the Extracellular Matrix. Semin Pediatr Neurol 2006;13:80–89.

    PubMed  Article  Google Scholar 

  11. Pan TC, Zhang RZ, Sudano DG, Marie SK, Bönnemann CG, Chu ML. New molecular mechanism for Ullrich congenital muscular dystrophy: a heterozygous in-Frame deletion in the COL6A1 gene causes a severe phenotype. Am J Hum Genet 2003;73:355–369.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  12. Ishikawa H, Sugie K, Murayama K, Awaya A, Suzuki Y, Noguchi S, et al. Ullrich disease due to deficiency of collagen VI in the sarcolemma. Neurology 2004;62:620–623.

    CAS  PubMed  Article  Google Scholar 

  13. Ishikawa H, Sugie K, Murayama K, Ito M, Minami N, Nishino I, et al. Ullrich disease: collagen VI deficiency: EM suggests a new basis for muscular weakness. Neurology 2002;59:920–923.

    CAS  PubMed  Article  Google Scholar 

  14. Voit T, Tome FM. The congenital muscular dystrophies. In: Engel AG, Franzini-Armstrong C, eds. Myology-basic and clinical, 3rd ed. New York: McGraw-Hill, 2004:1203–1238.

    Google Scholar 

  15. Bönnemann CG. The collagen VI-related myopathies: muscle meets its matrix. Nat Rev Neurol 2011;7:379–390.

    PubMed  Article  Google Scholar 

  16. Lampe AK, Dunn DM, von Niederhausern AC, Hamil C, Aoyagi A, Laval SH, et al. Automated genomic sequence analysis of the three collagen VI genes: applications to Ullrich congenital muscular dystrophy and Bethlem myopathy. J Med Genet 2005;42:108–120.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  17. Baker NL, Mörgelin M, Peat R, Goemans N, North KN, Bateman JF, et al. Dominant collagen VI mutations are a common cause of Ullrich congenital muscular dystrophy. Hum Mol Genet 2005;14:279–293.

    CAS  PubMed  Article  Google Scholar 

  18. Jimenez-Mallebrera C, Maioli MA, Kim J, Brown SC, Feng L, Lampe AK, et al. A comparative analysis of collagen VI production in muscle, skin and fibroblasts from 14 Ullrich congenital muscular dystrophy patients with dominant and recessive COL6A mutations. Neuromuscul Disord 2006;16:571–582.

    CAS  PubMed  Article  Google Scholar 

  19. Myllyharju J, Kivirikko KI. Collagens and collagen related diseases. Ann Med 2001;33:7–21.

    CAS  PubMed  Article  Google Scholar 

  20. Nadeau A, Kinali M, Main M, Jimenez-Mallebrera C, Aloysius A, Clement E, et al. Natural history of Ullrich congenital muscular dystrophy. Neurology 2009;73:25–31.

    CAS  PubMed  Article  Google Scholar 

  21. Foley AR, Hu Y, Zou Y, Yang M, Medne L, Leach M, et al. Large genomic deletions: a novel cause of Ullrich congenital muscular dystrophy. Ann Neurol 2011;69:206–211.

    CAS  PubMed  Article  Google Scholar 

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Affiliations

  1. Department of Pediatrics, Peking University First Hospital, Beijing, 100034, China

    Yan-Zhi Zhang, Hai-Po Yang, Ai-Jie Liu, Xing-Zhi Chang, Xi-Ru Wu & Hui Xiong

  2. Department of Neurology, Peking University First Hospital, Beijing, China

    Dan-Hua Zhao, Dao-Jun Hong & Yun Yuan

  3. Neuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke/NIH, Bethesda, USA

    Carsten Bonnemann

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  1. Yan-Zhi Zhang
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  2. Dan-Hua Zhao
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  8. Yun Yuan
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  9. Xi-Ru Wu
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  10. Hui Xiong
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Correspondence to Hui Xiong.

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Zhang, YZ., Zhao, DH., Yang, HP. et al. Novel collagen VI mutations identified in Chinese patients with Ullrich congenital muscular dystrophy. World J Pediatr 10, 126–132 (2014). https://doi.org/10.1007/s12519-014-0481-1

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  • DOI: https://doi.org/10.1007/s12519-014-0481-1

Key words

  • collagen VI
  • in-frame
  • missense
  • triple helical domain
  • Ullrich congenital muscular dystrophy