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 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.
Ouahchi
K
K
Institut de Génétique et de Biologie Moléculaire et Cellulaire (CNRS, INSERM, ULP), Illkirch, Strasbourg, France.
Arita
M
M
Kayden
H
H
Hentati
F
F
Ben Hamida
M
M
Sokol
R
R
Arai
H
H
Inoue
K
K
Mandel
J L
JL
Koenig
M
M
D000352:Africa, Northern / Q000453:epidemiology; D000595:Amino Acid Sequence; D001259:Ataxia / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics*; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D002874:Chromosome Mapping; D002898:Chromosomes, Human, Pair 8; D003718:Denmark / Q000453:epidemiology; D004739:England / Q000453:epidemiology; D005260:Female; D005602:France / Q000453:epidemiology; D005858:Germany / Q000453:epidemiology; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D012802:Sicily / Q000453:epidemiology; D014811:Vitamin E Deficiency / Q000235:genetics*
D002352:Carrier Proteins; C017763:alpha-tocopherol transfer protein