Chondroitin beta-1,4-N-acetylgalactosaminyltransferase-1 missense mutations are associated with neuropathies

Abstract

Chondroitin sulfate proteoglycans (CSPGs) in the peripheral nervous system likely participate as regulatory molecules in the process of axonal degeneration and regeneration. We investigated the chondroitin beta1,4-N- acetylgalactosaminyltransferase-1 (ChGn-1) gene in 114 patients affected with neuropathies including Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, hereditary motor and sensory neuropathy (HMSN) and unknown etiology. The controls were 196 patients with other neurological diseases. We found novel missense mutations in two patients with neuropathy (Bell's palsy, unknown HMSN) in exons 5 (H234R) and 10 (M509R), respectively. None of the patients with other neurological diseases had either of these mutations. We then synthesized the two soluble forms of ChGn-1, containing each of the above mutations. Each of the soluble mutants was expressed in COS-1 cells and the mutant proteins were purified. The purified mutant proteins were used for western blotting analysis using an anti-ChGn-1 antibody and evaluated for glycosyltransferase activities. Although the expression of the ChGn-1 mutant proteins was confirmed by western blotting, they exhibited no N-acetylgalactosamineT-II activities. It is possible that these mutations are associated with the pathogenetic mechanisms of the peripheral neuropathies. © 2011 The Japan Society of Human Genetics All rights reserved.