Ataxia with isolated vitamin E deficiency is caused by mutations in the alpha-tocopherol transfer protein.

Institut de Génétique et de Biologie Moléculaire et Cellulaire (CNRS, INSERM, ULP), Illkirch, Strasbourg, France.
Nature Genetics (Impact Factor: 29.65). 03/1995; 9(2):141-5. DOI: 10.1038/ng0295-141
Source: PubMed

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.

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