title: A novel GFAP mutation and disseminated white matter lesions: adult Alexander disease?
abstract: The recent discovery of heterozygous de novo mutations in the glial fibrillary acidic protein (GFAP) gene as the cause of infantile and juvenile Alexander disease has shed new light on the long-standing debate whether the adult subtype has the same etiology as infantile and juvenile Alexander disease. A 40-year-old man presented with subacute left hemiplegia and ataxia. Cranial MRI revealed disseminated patchy white matter changes involving the corpus callosum, basal ganglia and brainstem. CSF investigation demonstrated elevated total protein but was otherwise normal. Mutation analysis of the GFAP gene was performed in the patient, his mother and healthy brother. A novel heterozygous mutation in exon 4, 681G-->C, predicting an amino acid substitution E223Q in the rod region of GFAP was detected in the patient and his mother but not in his healthy brother or 150 control chromosomes. We conclude that the patient is actually afflicted with Alexander disease. Mutation analysis of GFAP should be considered in patients with remitting neurological deficits, disseminated white matter lesions and absence of inflammatory CSF changes.
authors.affiliation: Department of Pediatrics and Neuropediatrics, University of Göttingen, Göttingen, Germany. kbrock@med.uni-goettingen.de
authors.forename: Knut
authors.initials: K
authors.lastname: Brockmann
authors.forename: Moritz
authors.initials: M
authors.lastname: Meins
authors.forename: Angelika
authors.initials: A
authors.lastname: Taubert
authors.forename: Ralf
authors.initials: R
authors.lastname: Trappe
authors.forename: Martin
authors.initials: M
authors.lastname: Grond
authors.forename: Folker
authors.initials: F
authors.lastname: Hanefeld
mesh_terms: D000328:Adult; D017668:Age of Onset; D038261:Alexander Disease / Q000235:genetics*; D001369:Axons / Q000473:pathology*; D004252:DNA Mutational Analysis; D005091:Exons; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation; D016133:Polymerase Chain Reaction
chemical_list: D005904:Glial Fibrillary Acidic Protein