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 α–tocopherol into lipoproteins secreted by the liver, a function putatively attributable to the α–tocopherol transfer protein (α–TTP). Here we report the identification of three frame–shift mutations in the αTTP 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 αTTP gene mutations in AVED patients substantiates the therapeutic role of vitamin E as a protective agent against neurological damage in this disease.
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