title: GFAP mutations and polymorphisms in 13 unrelated Italian patients affected by Alexander disease.
abstract: 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.
authors: Laboratory of Molecular Genetics, G. Gaslini Institute, Genoa, Italy.
authors: F
authors: F
authors: Caroli
authors: R
authors: R
authors: Biancheri
authors: M
authors: M
authors: Seri
authors: A
authors: A
authors: Rossi
authors: A
authors: A
authors: Pessagno
authors: M
authors: M
authors: Bugiani
authors: F
authors: F
authors: Corsolini
authors: S
authors: S
authors: Savasta
authors: S
authors: S
authors: Romano
authors: C
authors: C
authors: Antonelli
authors: A
authors: A
authors: Romano
authors: D
authors: D
authors: Pareyson
authors: P
authors: P
authors: Gambero
authors: G
authors: G
authors: Uziel
authors: R
authors: R
authors: Ravazzolo
authors: I
authors: I
authors: Ceccherini
authors: M
authors: M
authors: Filocamo
mesh_terms: D000328:Adult; D038261:Alexander Disease / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D005820:Genetic Testing; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics*; D006801:Humans; D007558:Italy; D008297:Male; D008954:Models, Biological; D009154:Mutation; D020641:Polymorphism, Single Nucleotide
chemical_list: D005904:Glial Fibrillary Acidic Protein