1. Ataxia with isolated vitamin E deficiency is caused by mutations in the alpha-tocopherol transfer protein.
- Author
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Ouahchi K, Arita M, Kayden H, Hentati F, Ben Hamida M, Sokol R, Arai H, Inoue K, Mandel JL, and Koenig M
- Subjects
- Africa, Northern epidemiology, Amino Acid Sequence, Ataxia epidemiology, Base Sequence, Chromosome Mapping, Denmark epidemiology, England epidemiology, Female, France epidemiology, Germany epidemiology, Humans, Male, Molecular Sequence Data, Mutation, Pedigree, Sicily epidemiology, Ataxia etiology, Ataxia genetics, Carrier Proteins genetics, Chromosomes, Human, Pair 8, Vitamin E Deficiency genetics
- 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.
- Published
- 1995
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