title: Molecular genetic study in Japanese patients with Alexander disease: a novel mutation, R79L.
abstract: Since the first report by Brenner et al. of mutations in the glial fibrillary acidic protein (GFAP) gene in patients with Alexander disease, several molecular genetic studies have been performed in different ethnic groups. We previously reported a Japanese patient with a mutation, R239C, which is identical to one commonly found in American patients. Here we have analyzed four additional Japanese patients by screening for known mutations or, if no known mutation was found, by sequencing of all exons of the GFAP gene. We detected three missense mutations; one was a novel mutation, R79L, and two were previously reported mutations, R239C and R79C. All of our patients were heterozygous for their mutations. Together with the novel mutation, R79L, four different nucleotide changes altering the R79 residue have been reported, implying that any alternation of this arginine residue can give the GFAP protein a dominant negative effect, leading to accumulation of GFAP as Rosenthal fibers. We conclude that molecular genetic analysis of the GFAP gene is feasible for antemortem diagnosis of Alexander disease in Japanese patients.
authors.affiliation: Department of Inherited Metabolic Disease, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1, Tokyo, Japan
authors.forename: Naohide
authors.initials: N
authors.lastname: Shiroma
authors.forename: Naomi
authors.initials: N
authors.lastname: Kanazawa
authors.forename: Zenichiro
authors.initials: Z
authors.lastname: Kato
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Shimozawa
authors.forename: Atsushi
authors.initials: A
authors.lastname: Imamura
authors.forename: Masayuki
authors.initials: M
authors.lastname: Ito
authors.forename: Kyoich
authors.initials: K
authors.lastname: Ohtani
authors.forename: Akira
authors.initials: A
authors.lastname: Oka
authors.forename: Kazuyo
authors.initials: K
authors.lastname: Wakabayashi
authors.forename: Mizue
authors.initials: M
authors.lastname: Iai
authors.forename: Kenji
authors.initials: K
authors.lastname: Sugai
authors.forename: Masayuki
authors.initials: M
authors.lastname: Sasaki
authors.forename: Makiko
authors.initials: M
authors.lastname: Kaga
authors.forename: Takao
authors.initials: T
authors.lastname: Ohta
authors.forename: Seiichi
authors.initials: S
authors.lastname: Tsujino
mesh_terms: D038261:Alexander Disease / Q000175:diagnosis / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D004262:DNA Restriction Enzymes; D005260:Female; D005625:Frontal Lobe / Q000473:pathology; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007223:Infant; D007564:Japan; D008279:Magnetic Resonance Imaging; D008297:Male; D008967:Molecular Biology; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D016133:Polymerase Chain Reaction
chemical_list: D005904:Glial Fibrillary Acidic Protein; D004262:DNA Restriction Enzymes