Mutations associated with a childhood leukodystrophy, Alexander disease, cause deficiency in dimerization of the cytoskeletal protein GFAP

Abstract

Heterozygous, de novo mutations in the glial fibrillary acidic protein (GFAP) gene were recently found to be associated with Alexander disease. We examined the functional effect of such mutations, and observed a decrease in GFAP dimerization. This effect behaves in a dominant fashion and points towards a potential mechanism in pathogenesis.