ATAXIA WITH ISOLATED VITAMIN-E-DEFICIENCY IS CAUSED BY MUTATIONS IN THE ALPHA-TOCOPHEROL TRANSFER PROTEIN

Ataxia with isolated vitamin E deficiency (AVED) is an autosomal reces sive neurodegenerative disease which maps to chromosome 8q13. AVED pat ients have an impaired ability to incorporate a-tocopherol into lipopr oteins secreted by the liver, a function putatively attributable to th e a-tocopherol transfer protein (alpha-TTP). Here we report the identi fication of three frame-shift mutations in the alpha TTP gene. A 744de lA mutation accounts for 68% of the mutant alleles in the 17 families analysed and appears to have spread in North Africa and Italy. This mu tation correlates with a severe phenotype but alters only the C-termin al tenth of the protein. Two other mutations were found in single fami lies. The finding of alpha TTP gene mutations in AVED patients substan tiates the therapeutic role of vitamin E as a protective agent against neurological damage in this disease.