Fukuyama Congenital Muscular Dystrophy and Related Diseases

  • Motoi KanagawaEmail author
  • Hideki Tokuoka
  • Tatsushi Toda


A 1-year-old Japanese female patient with motor retardation was brought to our outpatient clinic by her mother. The child was found to have high serum creatine kinase (CK) level according to the 1-year-old medical checkup and was recommended further evaluation. The girl, the second child in her family, was born at full term in a local hospital and, after birth, was transferred to a general hospital because of muscle hypotonus, poor eye opening and sucking, and a high serum CK level (5461 IU/L: normal ranges are between 40 and 310 IU/L). She was followed up because her doctors considered these symptoms to arise from neonatal asphyxia. The infant developed quickly after 2 weeks, and her serum CK level decreased to normal. She grew up slightly slowly and acquired head control at 5 months of age (commonly acquired at 3–4 months after birth); she could not roll over at 7 months and rehabilitation was started. At 1 year of age, her muscle tonus remained decreased, and her serum CK level was elevated again (7532 IU/L). She could not stand up without support.


Muscular dystrophy Glycosylation Dystroglycanopathy Fukutin Ribitol phosphate 


  1. Briggs DC, Yoshida-Moriguchi T, Zheng T et al (2016) Structural basis of laminin binding to the LARGE glycans on dystroglycan. Nat Chem Biol 12:810–814CrossRefGoogle Scholar
  2. Fukuyama Y, Osawa M, Suzuki H (1981) Congenital progressive muscular dystrophy of the Fukuyama type – clinical, genetic and pathological considerations. Brain and Development 3:1–29CrossRefGoogle Scholar
  3. Gerin I, Ury B, Breloy I et al (2016) ISPD produces CDP-ribitol used by FKTN and FKRP to transfer ribitol phosphate onto α-dystroglycan. Nat Commun 7:11534CrossRefGoogle Scholar
  4. Godfrey C, Clement E, Mein R et al (2007) Refining genotype–phenotype correlations in muscular dystrophies with defective glycosylation of dystroglycan. Brain 130:2725–2735CrossRefGoogle Scholar
  5. Godfrey C, Foley AR, Clement E et al (2011) Dystroglycanopathies: coming into focus. Curr Opin Genet Dev 21:278–285CrossRefGoogle Scholar
  6. Hara Y, Balci-Hayta B, Yoshida-Moriguchi T et al (2011) A dystroglycan mutation associated with limb-girdle muscular dystrophy. N Engl J Med 364:939–946CrossRefGoogle Scholar
  7. Hayashi YK, Ogawa M, Tagawa K et al (2001) Selective deficiency of α-dystroglycan in Fukuyama-type congenital muscular dystrophy. Neurology 57:115–121CrossRefGoogle Scholar
  8. Inamori K, Yoshida-Moriguchi T, Hara Y et al (2012) Dystroglycan function requires xylosyl- and glucuronyltransferase activities of LARGE. Science 335:93–96CrossRefGoogle Scholar
  9. Kanagawa M, Saito F, Kunz S et al (2004) Molecular recognition by LARGE is essential for expression of functional dystroglycan. Cell 117:953–964CrossRefGoogle Scholar
  10. Kanagawa M, Yu CC, Ito C et al (2013) Impaired viability of muscle precursor cells in muscular dystrophy with glycosylation defects and amelioration of its severe phenotype by limited gene expression. Hum Mol Genet 22:3003–3015CrossRefGoogle Scholar
  11. Kanagawa M, Kobayashi K, Tajiri M et al (2016) Identification of a post-translational modification with ribitol-phosphate and its defect in muscular dystrophy. Cell Rep 14:2209–2223CrossRefGoogle Scholar
  12. Kobayashi K, Nakahori Y, Miyake M et al (1998) An ancient retrotransposal insertion causes Fukuyama-type congenital muscular dystrophy. Nature 394:388–392CrossRefGoogle Scholar
  13. Manya H, Chiba A, Yoshida A et al (2004) Demonstration of mammalian protein O-mannosyltransferase activity: coexpression of POMT1 and POMT2 required for enzymatic activity. Proc Natl Acad Sci U S A 101:500–505CrossRefGoogle Scholar
  14. Manya H, Yamaguchi Y, Kanagawa M et al (2016) The muscular dystrophy gene TMEM5 encodes a ribitol β1,4-xylosyltransferase required for the functional glycosylation of dystroglycan. J Biol Chem 291:24618–24627CrossRefGoogle Scholar
  15. Michele DE, Barresi R, Kanagawa M et al (2002) Post-translational disruption of dystroglycan-ligand interactions in congenital muscular dystrophies. Nature 418:417–422CrossRefGoogle Scholar
  16. Taniguchi-Ikeda M, Kobayashi K, Kanagawa M et al (2011) Pathogenic exon-trapping by SVA retrotransposon and rescue in Fukuyama muscular dystrophy. Nature 478:127–131CrossRefGoogle Scholar
  17. Watanabe M, Kobayashi K, Jin F et al (2005) Founder SVA retrotransposal insertion in Fukuyama-type congenital muscular dystrophy and its origin in Japanese and Northeast Asian populations. Am J Med Genet 138A:344–348CrossRefGoogle Scholar
  18. Yoshida A, Kobayashi K, Manya H et al (2001) Muscular dystrophy and neuronal migration disorder caused by mutations in a glycosyltransferase, POMGnT1. Dev Cell 1:717–724CrossRefGoogle Scholar
  19. Yoshida-Moriguchi T, Campbell KP (2015) Matriglycan: a novel polysaccharide that links dystroglycan to the basement membrane. Glycobiology 25:702–713CrossRefGoogle Scholar
  20. Yoshida-Moriguchi T, Willer T, Anderson ME et al (2013) SGK196 is a glycosylation-specific O-mannose kinase required for dystroglycan function. Science 341:896–899CrossRefGoogle Scholar

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© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Division of Neurology/Molecular Brain ScienceKobe University Graduate School of MedicineKobeJapan
  2. 2.Department of Neurology, Division of Neuroscience, Graduate School of MedicineThe University of TokyoTokyoJapan

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