title: A novel mutation in glial fibrillary acidic protein gene in a patient with Alexander disease.
abstract: Alexander disease is a rare, progressive, leukoencephalopathy whose hallmark is the widespread accumulation of Rosenthal fibers. The most common form affects infants and young children, and is characterized by progressive failure of central myelination, usually leading to death before adulthood. Definitive diagnosis of Alexander disease has required biopsy or autopsy to demonstrate the presence of Rosenthal fibers. However, missense mutations in the coding region of the glial fibrillary acidic protein (GFAP) gene have recently been associated with a high percentage of pathologically proven cases. Here we report that a 10-year-old Japanese patient who showed clinical signs of Alexander disease is heterozygous for a C to T transition in which predicts a novel A244V amino acid substitution in the conserved 2A alpha-helix domain of GFAP. The nucleotide change was not found in 65 normal individuals (130 alleles). These results provide further support for a causative role for GFAP mutations in Alexander disease, and suggest DNA sequencing as an alternative diagnostic to biopsy.
authors.affiliation: Department of Medical Genetics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Sendai 980-8574, Japan. aokiy@mail.cc.tohoku.ac.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Aoki
authors.forename: K
authors.initials: K
authors.lastname: Haginoya
authors.forename: M
authors.initials: M
authors.lastname: Munakata
authors.forename: H
authors.initials: H
authors.lastname: Yokoyama
authors.forename: T
authors.initials: T
authors.lastname: Nishio
authors.forename: N
authors.initials: N
authors.lastname: Togashi
authors.forename: T
authors.initials: T
authors.lastname: Ito
authors.forename: Y
authors.initials: Y
authors.lastname: Suzuki
authors.forename: S
authors.initials: S
authors.lastname: Kure
authors.forename: K
authors.initials: K
authors.lastname: Iinuma
authors.forename: M
authors.initials: M
authors.lastname: Brenner
authors.forename: Y
authors.initials: Y
authors.lastname: Matsubara
mesh_terms: D000409:Alanine / Q000235:genetics / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology*; D002648:Child; D004252:DNA Mutational Analysis; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics* / Q000378:metabolism; D020279:Hereditary Central Nervous System Demyelinating Diseases / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology*; D006579:Heterozygote; D006801:Humans; D007564:Japan; D008279:Magnetic Resonance Imaging; D008297:Male; D020125:Mutation, Missense / Q000235:genetics*; D017434:Protein Structure, Tertiary / Q000235:genetics; D014055:Tomography, Emission-Computed; D014633:Valine / Q000235:genetics / Q000378:metabolism
chemical_list: D005904:Glial Fibrillary Acidic Protein; D014633:Valine; D000409:Alanine