Integrin alpha 7 beta 1 in muscular dystrophy/myopathy of unknown etiology

Am J Pathol. 2002 Jun;160(6):2135-43. doi: 10.1016/s0002-9440(10)61162-5.


To investigate the role of integrin alpha 7 in muscle pathology, we used a "candidate gene" approach in a large cohort of muscular dystrophy/myopathy patients. Antibodies against the intracellular domain of the integrin alpha 7A and alpha 7B were used to stain muscle biopsies from 210 patients with muscular dystrophy/myopathy of unknown etiology. Levels of alpha 7A and alpha 7B integrin were found to be decreased in 35 of 210 patients (approximately 17%). In six of these patients no integrin alpha 7B was detected. Screening for alpha 7B mutation in 30 of 35 patients detected only one integrin alpha 7 missense mutation (the mutation on the second allele was not found) in a patient presenting with a congenital muscular dystrophy-like phenotype. No integrin alpha 7 gene mutations were identified in all of the other patients showing integrin alpha 7 deficiency. In the process of mutation analysis, we identified a novel integrin alpha 7 isoform presenting 72-bp deletion. This isoform results from a partial deletion of exon 21 due to the use of a cryptic splice site generated by a G to A missense mutation at nucleotide position 2644 in integrin alpha 7 cDNA. This spliced isoform is present in about 12% of the chromosomes studied. We conclude that secondary integrin alpha 7 deficiency is rather common in muscular dystrophy/myopathy of unknown etiology, emphasizing the multiple mechanisms that may modulate integrin function and stability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing
  • Biopsy
  • Child
  • Child, Preschool
  • Down-Regulation
  • Female
  • Fluorescent Antibody Technique
  • Humans
  • Infant
  • Integrins / deficiency
  • Integrins / genetics
  • Integrins / physiology*
  • Male
  • Muscles / pathology
  • Muscular Diseases / pathology
  • Muscular Diseases / physiopathology*
  • Muscular Dystrophies / pathology
  • Muscular Dystrophies / physiopathology*
  • Mutation
  • Mutation, Missense
  • Oligonucleotide Array Sequence Analysis
  • Polymorphism, Single-Stranded Conformational
  • RNA, Messenger / metabolism
  • Restriction Mapping
  • Reverse Transcriptase Polymerase Chain Reaction


  • Integrins
  • RNA, Messenger
  • integrin alpha7beta1