A novel mutation in glial fibrillary acidic protein gene in a patient with Alexander disease

Neurosci Lett. 2001 Oct 19;312(2):71-4. doi: 10.1016/s0304-3940(01)02139-5.


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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine / genetics
  • Alanine / metabolism
  • Brain / diagnostic imaging
  • Brain / pathology*
  • Child
  • DNA Mutational Analysis
  • Gene Frequency / genetics
  • Genetic Predisposition to Disease / genetics
  • Genetic Testing
  • Glial Fibrillary Acidic Protein / genetics*
  • Glial Fibrillary Acidic Protein / metabolism
  • Hereditary Central Nervous System Demyelinating Diseases / diagnostic imaging
  • Hereditary Central Nervous System Demyelinating Diseases / genetics*
  • Hereditary Central Nervous System Demyelinating Diseases / pathology*
  • Heterozygote
  • Humans
  • Japan
  • Magnetic Resonance Imaging
  • Male
  • Mutation, Missense / genetics*
  • Protein Structure, Tertiary / genetics
  • Tomography, Emission-Computed
  • Valine / genetics
  • Valine / metabolism


  • Glial Fibrillary Acidic Protein
  • Valine
  • Alanine