Integrin α7β1 in muscular dystrophy/myopathy of unknown etiology

To investigate the role of integrin α7 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 α7A and α7B were used to stain muscle biopsies from 210 patients with muscular dystrophy/myopathy of unknown etiology. Levels of α7A and α7B integrin were found to be decreased in 35 of 210 patients (∼17%). In six of these patients no integrin α7B was detected. Screening for α7B mutation in 30 of 35 patients detected only one integrin α7 missense mutation (the mutation on the second allele was not found) in a patient presenting with a congenital muscular dystrophy-like phenotype. No integrin α7 gene mutations were identified in all of the other patients showing integrin α7 deficiency. In the process of mutation analysis, we identified a novel integrin α7 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 α7 cDNA. This spliced isoform is present in about 12% of the chromosomes studied. We conclude that secondary integrin α7 deficiency is rather common in muscular dystrophy/myopathy of unknown etiology, emphasizing the multiple mechanisms that may modulate integrin function and stability.