Mutations in the integrin α7 gene cause congenital myopathy

The basal lamina of muscle fibers plays a crucial role in the of development and function of skeletal muscle. An important laminin receptor in muscle is integrin alpha 7 beta 1D. Integrin beta 1 is expressed throughout the body, while integrin alpha 7 is more muscle-specific(1-5). To address the role of integrin alpha 7 in human muscle disease, we determined alpha 7 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 alpha 7 deficiency and normal laminin alpha 2 chain expression. To determine nine if any of these three patients had mutations of the integrin alpha 7 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 l-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.