Giant axonal neuropathy (GAN, MIM: 256850) is a devastating autosomal recessive 
disorder characterized by an early onset severe peripheral neuropathy, varying 
central nervous system involvement and strikingly frizzly hair. Giant axonal 
neuropathy is usually caused by mutations in the gigaxonin gene (GAN) but 
genetic heterogeneity has been demonstrated for a milder variant of this 
disease. Here, we report ten patients referred to us for molecular genetic 
diagnosis. All patients had typical clinical signs suggestive of giant axonal 
neuropathy. In seven affected individuals, we found disease causing mutations in 
the gigaxonin gene affecting both alleles: two splice-site and four missense 
mutations, not reported previously. Gigaxonin binds N-terminally to ubiquitin 
activating enzyme E1 and C-terminally to various microtubule associated proteins 
causing their ubiquitin mediated degradation. It was shown for a number of 
gigaxonin mutations that they impede this process leading to accumulation of 
microtubule associated proteins and there by impairing cellular functions.