title: Identification of seven novel mutations in the GAN gene.
abstract: Giant axonal neuropathy (GAN) is a severe early onset neurodegenerative disorder affecting both the peripheral nerves and the central nervous system. The diagnosis is based on the presence of characteristic giant axons on nerve biopsy. In GAN, the integrity of the intermediate filament network is altered. Indeed, abnormal accumulation of the intermediate filaments has been reported in different cell types, including in the swollen axons, which are filled with neurofilaments. We identified the defective protein, gigaxonin, of unknown function, and reported fourteen distinct mutations in twelve families of various origins. Two additional mutations have been recently reported. In the present study, we analysed the GAN gene in 6 families, and identified seven novel mutations: three nonsense and two missense mutations and two deletions. In addition, the molecular result for an already reported family was re-evaluated. In this family, the R269Q "polymorphism" is in fact the pathogenic mutation.
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch Cedex, C.U. de Strasbourg, France.
authors.forename: P
authors.initials: P
authors.lastname: Bomont
authors.forename: C
authors.initials: C
authors.lastname: Ioos
authors.forename: C
authors.initials: C
authors.lastname: Yalcinkaya
authors.forename: R
authors.initials: R
authors.lastname: Korinthenberg
authors.forename: J M
authors.initials: JM
authors.lastname: Vallat
authors.forename: S
authors.initials: S
authors.lastname: Assami
authors.forename: A
authors.initials: A
authors.lastname: Munnich
authors.forename: B
authors.initials: B
authors.lastname: Chabrol
authors.forename: G
authors.initials: G
authors.lastname: Kurlemann
authors.forename: M
authors.initials: M
authors.lastname: Tazir
authors.forename: M
authors.initials: M
authors.lastname: Koenig
mesh_terms: D017668:Age of Onset; D019943:Amino Acid Substitution / Q000235:genetics; D002675:Child, Preschool; D003598:Cytoskeletal Proteins / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D008040:Genetic Linkage / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype
chemical_list: D003598:Cytoskeletal Proteins; C416508:GAN protein, human