Clinical and genetic study in Chinese patients with Alexander disease

Alexander disease is a rare progressive leukoencephalopathy inherited in an autosomal dominant manner. The infantile form is the most common, with onset before 2 years of age. The typical clinical signs include psychomotor retardation and regression, seizures, and megalencephaly. Juvenile and adult forms are also recognized. The neuropathology of Alexander disease is characterized by abundant presence of Rosenthal fibers in astrocytes in the brain. GFAP has been identified to be the only gene associated with Alexander disease since 2001. Only 1 patient with Alexander disease confirmed by genetic testing has been reported in mainland China. To get further information of the clinical and genetic characteristics of Chinese patients, we analyzed an additional 3 cases with the infantile or juvenile form. A novel mutation, Y83H, and a previously reported mutation, R88C, were identified in these patients. Both mutations were heterozygous and de novo. The results of this research expand the number of patients with Alexander disease found to have GFAP coding mutations in mainland China. A novel missense mutation, Y83H, is identified.