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 α-tocopherol transfer protein (αTTP). We have cloned the cDNA and several genomic phage clones covering the entire human αTTP gene and determined the junctions between the five exons and four introns that composed the gene for human αTTP. 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 αTTP. 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 αTTP in AVED.
ASJC Scopus subject areas
- Clinical Neurology