Advertisement

Fukutin and Fukuyama Congenital Muscular Dystrophy

  • Motoi Kanagawa
  • Tatsushi Toda

Abstract

Recent genetic and biochemical studies have revealed that mutations in (putative) glycosyltransferases and subsequent abnormal glycosylation of dystroglycan are associated with several forms of congenital muscular dystrophies (Kanagawa and Toda 2006). Fukuyama congenital muscular dystrophy (FCMD), the second most common childhood muscular dystrophy in Japan, is one of the congenital muscular dystrophies displaying glycosylation defects of α-dystroglycan. The gene responsible for this disease is fukutin, and its protein product is assumed to participate in cellular glycosylation events. FCMD is characterized by severe congenital muscular dystrophy, abnormal neuronal migration associated with mental retardation and epilepsy, and frequent eye abnormalities. Therefore, fukutin-dependent glycosylation of α-dystroglycan plays crucial roles in structural/functional maintenance of skeletal muscle, central/peripheral nervous system, and eye. α-Dystroglycan, a highly glycosylated protein, forms a protein complex with β-dystroglycan, and the dystroglycan complex links laminin in the extracellular matrix to the cellular actin cytoskeleton. Abnormal glycosylation of α-dystroglycan results in a severe reduction in laminin-binding activity, and thus disruption of the interaction between dystroglycan and laminin caused by fukutin mutations is believed to be the major cause of FCMD.

Keywords

Muscular Dystrophy Congenital Muscular Dystrophy Muscle Cell Membrane Abnormal Glycosylation Muscle Plasma Membrane 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Barresi R, Michele DE, Kanagawa M, Harper HA, Dovico SA, Satz JS, Moore SA, Zhang W, Schachter H, Dumanski JP, Cohn RD, Nishino I, Campbell KP (2004) LARGE can functionally bypass alpha-dystroglycan glycosylation defects in distinct congenital muscular dystrophies. Nat Med 10:696–703PubMedCrossRefGoogle Scholar
  2. Kanagawa M, Toda T (2006) The genetic and molecular basis of muscular dystrophy: roles of cell-matrix linkage in the pathogenesis. J Hum Genet 51:915–926PubMedCrossRefGoogle Scholar
  3. Kobayashi K, Nakahori Y, Miyake M, Matsumura K, Kondo-Iida E, Nomura Y, Segawa M, Yoshioka M, Saito K, Osawa M, Hamano K, Sakakihara Y, Nonaka I, Nakagome Y, Kanazawa I, Nakamura Y, Tokunaga K, Toda T (1998) An ancient retrotransposal insertion causes Fukuyama-type congenital muscular dystrophy. Nature 394:388–392PubMedCrossRefGoogle Scholar
  4. Michele DE, Barresi R, Kanagawa M, Saito F, Cohn RD, Satz JS, Dollar J, Nishino I, Kelley RI, Somer H, Straub V, Mathews KD, Moore SA, Campbell KP (2002) Post-translational disruption of dystroglycan-ligand interactions in congenital muscular dystrophies. Nature 418:417–422PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2008

Authors and Affiliations

  • Motoi Kanagawa
    • 1
  • Tatsushi Toda
    • 1
  1. 1.Division of Clinical Genetics, Department of Medical GeneticsOsaka University Graduate School of MedicineSuita, OsakaJapan

Personalised recommendations