Molecular genetic study in Japanese patients with Alexander disease: a novel mutation, R79L.
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.
Shiroma
Naohide
N
Department of Inherited Metabolic Disease, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1, Tokyo, Japan
Kanazawa
Naomi
N
Kato
Zenichiro
Z
Shimozawa
Nobuyuki
N
Imamura
Atsushi
A
Ito
Masayuki
M
Ohtani
Kyoich
K
Oka
Akira
A
Wakabayashi
Kazuyo
K
Iai
Mizue
M
Sugai
Kenji
K
Sasaki
Masayuki
M
Kaga
Makiko
M
Ohta
Takao
T
Tsujino
Seiichi
S
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
D005904:Glial Fibrillary Acidic Protein; D004262:DNA Restriction Enzymes