title: An autopsied case of adult-onset bulbospinalform Alexander disease with a novel S393R mutation in the GFAP gene.
abstract: A 50-year-old Japanese man with no apparent family history noticed diplopia. He gradually showed gait disturbance and dysuria. Abducens disorder of eye movement with nystagmus, tongue atrophy with fasciculation, spastic tetraparesis, and sensory disturbance were also observed. MRI showed severe atrophy of the medulla oblongata to the cervical cord ("tadpole appearance"). Tracheotomy and gastrostomy were performed 7 years after onset due to the development of bulbar palsy. Death occurred following respiratory failure after 11 years total disease duration. The brain weighed 1,380 g. The cerebrum, cerebellum, midbrain, and upper pons were preserved from atrophy, but the medulla oblongata to the cervical cord showed severe atrophy. A few Rosenthal fibers were observed in the cerebral white matter, basal ganglia, and cerebellum, whereas numerous Rosenthal fibers were observed in the medulla oblongata to the cervical cord. Myelin loss with relatively preserved axons was extensively observed from the middle of the pons to the spinal cord. The clinicopathological diagnosis was adult-onset bulbospinal-form Alexander disease. Glial fibrillary acidic protein (GFAP) gene analysis revealed a novel mutation of S393R. Expression patterns of S393R mutant GFAP using adrenal carcinoma-derived cells (SW13 cells) showed a decreased number of filamentous structures and abnormal aggregates.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Iwasaki
authors.forename: Yufuko
authors.initials: Y
authors.lastname: Saito
authors.forename: Keiko
authors.initials: K
authors.lastname: Mori
authors.forename: Masumi
authors.initials: M
authors.lastname: Ito
authors.forename: Maya
authors.initials: M
authors.lastname: Mimuro
authors.forename: Ikuko
authors.initials: I
authors.lastname: Aiba
authors.forename: Kozo
authors.initials: K
authors.lastname: Saito
authors.forename: Ikuko
authors.initials: I
authors.lastname: Mizuta
authors.forename: Tomokatsu
authors.initials: T
authors.lastname: Yoshida
authors.forename: Masanori
authors.initials: M
authors.lastname: Nakagawa
authors.forename: Mari
authors.initials: M
authors.lastname: Yoshida
mesh_terms: D017668:Age of Onset; D038261:Alexander Disease / Q000235:genetics* / Q000473:pathology*; D001344:Autopsy; D002574:Cervical Vertebrae; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics*; D006801:Humans; D008297:Male; D008526:Medulla Oblongata / Q000473:pathology; D008875:Middle Aged; D017354:Point Mutation; D013116:Spinal Cord / Q000473:pathology
chemical_list: D005904:Glial Fibrillary Acidic Protein