title: Human alpha-tocopherol transfer protein: gene structure and mutations in familial vitamin E deficiency.
abstract: Familial vitamin E deficiency (AVED) causes ataxia and peripheral neuropathy that resembles Friedreich's ataxia. AVED is thought to be caused by a defect in the transport of vitamin E in liver cells, which is the probable function of alpha-tocopherol transfer protein (alphaTTP). We have cloned the cDNA and several genomic phage clones covering the entire human alphaTTP gene and determined the junctions between the five exons and four introns that composed the gene for human alphaTTP. Three mutations in three unrelated North American families with AVED were identified. Two mutations, 485delT and 513insTT, cause a frame shift and a premature stop codon and the third mutation 574G-->A would substitute Arg192 to His in alphaTTP. The 2 patients with a severe form of AVED were homozygous with 485delT and 513insTT, respectively, while the patient with a mild form of the disease was compound heterozygous with 513insTT and 574G-->A. These findings have identified the underlying genetic defect in AVED and have confirmed the role of alphaTTP in AVED.
authors.affiliation: Department of Neurology, Northwestern University Medical School, Chicago, Illinois 60611, USA.
authors.forename: A
authors.initials: A
authors.lastname: Hentati
authors.forename: H X
authors.initials: HX
authors.lastname: Deng
authors.forename: W Y
authors.initials: WY
authors.lastname: Hung
authors.forename: M
authors.initials: M
authors.lastname: Nayer
authors.forename: M S
authors.initials: MS
authors.lastname: Ahmed
authors.forename: X
authors.initials: X
authors.lastname: He
authors.forename: R
authors.initials: R
authors.lastname: Tim
authors.forename: D A
authors.initials: DA
authors.lastname: Stumpf
authors.forename: T
authors.initials: T
authors.lastname: Siddique
authors.lastname: Ahmed
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D002898:Chromosomes, Human, Pair 8; D003001:Cloning, Molecular; D018388:Codon, Terminator; D017931:DNA Primers; D018076:DNA, Complementary; D005091:Exons; D006580:Genetic Carrier Screening; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D012347:RNA, Transfer, Arg; D014810:Vitamin E / Q000235:genetics*; D014811:Vitamin E Deficiency / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; D018388:Codon, Terminator; D017931:DNA Primers; D018076:DNA, Complementary; D012347:RNA, Transfer, Arg; C017763:alpha-tocopherol transfer protein; D014810:Vitamin E