Integrin α7β1 in muscular dystrophy/myopathy of unknown etiology

To investigate the role of integrin alpha7 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 alpha7A and alpha7B were used to stain muscle biopsies from 210 patients with muscular dystrophy/myopathy of unknown etiology. Levels of alpha7A and alpha7B integrin were found to be decreased in 35 of 210 patients (similar to17%). In six of these patients no integrin alpha7B was detected. Screening for alpha7B mutation in 30 of 35 patients detected only one integrin alpha7 missense mutation (the mutation on the second allele was not found) in a patient presenting with a congenital muscular dystrophy-like phenotype. No integrin alpha7 gene mutations were identified in all of the other patients showing integrin alpha7 deficiency. in the process of mutation analysis, we identified a novel integrin alpha7 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 alpha7 cDNA. This spliced isoform is present in about 12% of the chromosomes studied. We conclude that secondary integrin alpha7 deficiency is rather common in muscular dystrophy/myopathy of unknown etiology, emphasizing the multiple mechanisms that may modulate integrin function and stability.