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Mutations in the integrin α7 gene cause congenital myopathy

Nature Genetics volume 19, pages 94–97 (1998)Cite this article

Abstract

The basal lamina of muscle fibers plays a crucial role in the development and function of skeletal muscle. An important laminin receptor in muscle is integrin α7β1D. Integrin β1 is expressed throughout the body, while integrin α7 is more muscle-specific1–5. To address the role of integrin α7 in human muscle disease, we determined α7 protein expression in muscle biopsies from 117 patients with unclassified congenital myopathy and congenital muscular dystrophy by immunocytochemistry. We found three unrelated patients with integrin α7 deficiency and normal laminin α2 chain expression. To determine if any of these three patients had mutations of the integrin α7 gene, ITGA7, we cloned and sequenced the full-length human ITGA7 cDNA, and screened the patients for mutations. One patient had splice mutations on both alleles; one causing a 21 -bp insertion in the conserved cysteine-rich region, and the other causing a 98-bp deletion. A second patient was a compound heterozygote for the same 98-bp deletion, and had a 1-bp frame-shift deletion on the other allele. A third showed marked deficiency of ITGA7 mRNA. Clinically, these patients showed congenital myopathy with delayed motor milestones. Our results demonstrate that mutations in ITGA7 are involved in a form of congenital myopathy.

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Authors and Affiliations

  1. Department ofNeuromuscular Research, National Institute ofNeuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, 187-8502, Japan

    Yukiko K. Hayashi, Megumu Ogawa, Chie Matsuda, Toshifumi Tsukahara & Kiichi Arahata

  2. Department of Molecular Genetics and Biochemistry, Department of Human Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, 15261, USA

    Fan-Li Chou, Jian-zhou Wang & Eric P. Hoffman

  3. The Burnham Institute, La Jolla Cancer Research Center, La Jolla, California, 92037, USA

    Eva Engvall

  4. Department of Biomolecular Engineering, National Institute of Bioscience and Human Technology, Agency of Industrial Science and Technology, Tsukuba, Ibaraki, 305, Japan

    Chie Matsuda

  5. Department of Pediatrics, Nagano Children's Hospital, MinamiAzumi, Nagano, 399-8205, Japan

    Shinichi Hirabayashi

  6. Department of Neuropediatrics, Seirei Mikatabara Hospital, Hamamatsu, Shizuoka, 433-8105, Japan

    Kenji Yokochi

  7. Department of Stomatology, University of California San Francisco, San Francisco, California, 94143, USA

    Barry L. Ziober & Randall H. Kramer

  8. Department of Cell and Structural Biology, University of Illinois, Urbana, Illinois, 61801, USA

    Stephen J. Kaufman

  9. Department of Cell Biology National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, 187-8502, Japan

    Eijiro Ozawa

  10. Department ofUltrastructural Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, 187-8502, Japan

    Yu-ichi Goto & Ikuya Nonaka

Authors
  1. Yukiko K. Hayashi
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Correspondence to Kiichi Arahata.

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Hayashi, Y., Chou, FL., Engvall, E. et al. Mutations in the integrin α7 gene cause congenital myopathy. Nat Genet 19, 94–97 (1998). https://doi.org/10.1038/ng0598-94

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