title: Ataxia with isolated vitamin E deficiency is caused by mutations in the alpha-tocopherol transfer protein.
abstract: Ataxia with isolated vitamin E deficiency (AVED) is an autosomal recessive neurodegenerative disease which maps to chromosome 8q13. AVED patients have an impaired ability to incorporate alpha-tocopherol into lipoproteins secreted by the liver, a function putatively attributable to the alpha-tocopherol transfer protein (alpha-TTP). Here we report the identification of three frame-shift mutations in the alpha TTP gene. A 744delA mutation accounts for 68% of the mutant alleles in the 17 families analysed and appears to have spread in North Africa and Italy. This mutation correlates with a severe phenotype but alters only the C-terminal tenth of the protein. Two other mutations were found in single families. The finding of alpha TTP gene mutations in AVED patients substantiates the therapeutic role of vitamin E as a protective agent against neurological damage in this disease.
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire (CNRS, INSERM, ULP), Illkirch, Strasbourg, France.
authors.forename: K
authors.initials: K
authors.lastname: Ouahchi
authors.forename: M
authors.initials: M
authors.lastname: Arita
authors.forename: H
authors.initials: H
authors.lastname: Kayden
authors.forename: F
authors.initials: F
authors.lastname: Hentati
authors.forename: M
authors.initials: M
authors.lastname: Ben Hamida
authors.forename: R
authors.initials: R
authors.lastname: Sokol
authors.forename: H
authors.initials: H
authors.lastname: Arai
authors.forename: K
authors.initials: K
authors.lastname: Inoue
authors.forename: J L
authors.initials: JL
authors.lastname: Mandel
authors.forename: M
authors.initials: M
authors.lastname: Koenig
mesh_terms: D000352:Africa, Northern / Q000453:epidemiology; D000595:Amino Acid Sequence; D001259:Ataxia / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics*; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D002874:Chromosome Mapping; D002898:Chromosomes, Human, Pair 8; D003718:Denmark / Q000453:epidemiology; D004739:England / Q000453:epidemiology; D005260:Female; D005602:France / Q000453:epidemiology; D005858:Germany / Q000453:epidemiology; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D012802:Sicily / Q000453:epidemiology; D014811:Vitamin E Deficiency / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; C017763:alpha-tocopherol transfer protein