GFAP mutations and polymorphisms in 13 unrelated Italian patients affected by Alexander disease

Clin Genet. 2007 Nov;72(5):427-33. doi: 10.1111/j.1399-0004.2007.00869.x. Epub 2007 Sep 25.


Alexander disease (AD), a rare neurodegenerative disorder of the central nervous system, is characterized by the accumulation of cytoplasmic protein aggregates (Rosenthal fibers) composed of glial fibrillary acidic protein (GFAP) and small heat-shock proteins within astrocytes. To date, more than 40 different GFAP mutations have been reported in AD. The present study is aimed at the molecular diagnosis of Italian patients suspected to be affected by AD. By analyzing the GFAP gene of 13 unrelated patients (eight with infantile form, two with juvenile form and three with adult form), we found 11 different alleles, including four new ones. Among the novel mutations, three (p.R70Q, p.R73K, and p.R79P) were identified in exon 1 and p.L359P in exon 6. The sequence analysis also detected six different single nucleotide polymorphic variants, including two previously unreported ones, spread throughout non-coding regions (introns 2, 3, 5, 6, and 3'UTR) of the gene. All patients were heterozygous for the mutations, thus confirming their dominant effect.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alexander Disease / genetics*
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • Female
  • Genetic Testing
  • Glial Fibrillary Acidic Protein / genetics*
  • Humans
  • Italy
  • Male
  • Models, Biological
  • Mutation*
  • Polymorphism, Single Nucleotide*


  • Glial Fibrillary Acidic Protein