Molecular genetic study in Japanese patients with Alexander disease: a novel mutation, R79L

Brain Dev. 2003 Mar;25(2):116-21. doi: 10.1016/s0387-7604(02)00167-5.


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.

MeSH terms

  • Alexander Disease / diagnosis
  • Alexander Disease / genetics*
  • Asian People / genetics*
  • Base Sequence / genetics
  • Child
  • Child, Preschool
  • DNA Restriction Enzymes
  • Female
  • Frontal Lobe / pathology
  • Glial Fibrillary Acidic Protein / genetics*
  • Heterozygote
  • Humans
  • Infant
  • Japan
  • Magnetic Resonance Imaging
  • Male
  • Molecular Biology
  • Molecular Sequence Data
  • Mutation, Missense*
  • Polymerase Chain Reaction


  • Glial Fibrillary Acidic Protein
  • DNA Restriction Enzymes