A mutation in the α tropomyosin gene TPM3 associated with autosomal dominant nemaline myopathy

Abstract

Nemaline myopathies are diseases characterized by the presence in muscle fibres of pathognomonic rod bodies. These are composed largely of −actinin and actin. We have identified a missense mutation in the −tropomyosin gene, TPM3, which segregates completely with the disease in a family whose autosomal dominant nemaline myopathy we had previously localized to chromosome 1p13−q25. The mutation substitutes an arginine residue for a highly conserved methionine in a putative actin−binding site near the N terminus of the −tropomyosin. The mutation may strengthen tropomyosin − actin binding, leading to rod body formation, by adding a further basic residue to the postulated actin−binding motif.