Asymptomatic hereditary Alexander's disease caused by a novel mutation in GFAP

J Neurol Sci. 2004 Oct 15;225(1-2):125-7. doi: 10.1016/j.jns.2004.07.008.


We report on a family with dominantly inherited asymptomatic Alexander's disease due to a novel Glial fibrillary acidic protein (GFAP) mutation. The proband, a 16-month-old boy, presented with megalocephaly and brain magnetic resonance imaging (MRI) showing the typical findings of Alexander's disease. Molecular analysis showed that he was a heterozygote of the L331P mutation of GFAP. His mother and sister, without megalocephaly or other neurological abnormalities, were also heterozygotes of the mutation and their brain magnetic resonance imaging showed mild changes in the caudates and deep frontal white matters. These results suggest the existence of a forme fruste of Alexander's disease. The L331P mutation may be associated with the mild phenotype of Alexander's disease. To elucidate the genotype-phenotype correlation in Alexander's disease, molecular diagnosis and MRI examination are required for many patients and their families.

Publication types

  • Case Reports
  • Comparative Study

MeSH terms

  • Alexander Disease / genetics*
  • Brain / pathology
  • Child
  • DNA Mutational Analysis / methods
  • Exons
  • Female
  • Glial Fibrillary Acidic Protein / genetics*
  • Humans
  • Infant
  • Leucine / genetics
  • Magnetic Resonance Imaging / methods
  • Male
  • Mutation*
  • Proline / genetics
  • RNA, Messenger / biosynthesis
  • Reverse Transcriptase Polymerase Chain Reaction / methods


  • Glial Fibrillary Acidic Protein
  • RNA, Messenger
  • Proline
  • Leucine