Giant axonal neuropathy: an inborn error of organization of intermediate filaments

Light microscopic examination of cultured skin fibroblasts from three patients with giant axonal neuropathy (GAN) revealed large aggregates of intermediate filaments (IF). However, electrophoretic analysis of these cells showed normal amounts of vimentin, the fibroblast IF subunit protein. The isoelectric point and peptide mapping of vimentin were identical to controls. Moreover, vimentin was synthesized and phosphorylated at a normal rate. These findings demonstrate that GAN is an inborn error of the organization of IF and suggest that the basic genetic defect in GAN does not involve primarily the IF subunit proteins.