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http://purl.uniprot.org/citations/7566022http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/7566022http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/7566022http://www.w3.org/2000/01/rdf-schema#comment"

Background

Patients with isolated vitamin E deficiency have an impaired ability to incorporate alpha-tocopherol into lipoproteins in the liver and usually have symptoms and signs of spinocerebellar dysfunction before adolescence. Accumulated evidence suggests that the alpha-tocopherol-transfer protein, which is presumed to function in the intracellular transport of alpha-tocopherol, is abnormal in these patients.

Methods

We studied a patient from an isolated Japanese island who began to have ataxia, dysarthria, and sensory disturbances in the sixth decade of life. His serum vitamin E concentration was low (1.2 micrograms per milliliter [2.8 mumol per liter]). Exons of his gene for the alpha-tocopherol-transfer protein were analyzed by DNA sequencing. We also screened an additional 801 inhabitants of the island for the mutation. Both the normal and mutant alpha-to-copherol-transfer proteins were expressed in COS-7 cells and studied by immunoblot analysis and assay for alpha-tocopherol-transfer activity.

Results

The patient was homozygous for a point mutation that replaces histidine (CAT) with glutamine (CAG) at position 101 of the gene for the alpha-tocopherol-transfer protein. When expressed in COS-7 cells, the missense mutation produced a functionally defective alpha-tocopherol-transfer protein with approximately 11 percent of the transfer activity of the wild-type protein. Of the 801 island inhabitants examined, 21 were heterozygous for the His101Gln mutation. In all affected subjects, including the patient, this mutation cosegregated with an intron-sequence polymorphism. The heterozygotes were phenotypically normal and had serum vitamin E concentrations that were on average 25 percent lower than those of normal subjects (mean [+/- SD], 7.5 +/- 2.2 vs. 10.1 +/-2.8 micrograms per milliliter [17.4 +/- 5.1 vs. 23.4 +/-6.5 mumol per liter]; P = 0.002).

Conclusions

alpha-Tocopherol-transfer protein is a determinant of serum vitamin E concentrations. An abnormality in this protein is a cause of spinocerebellar dysfunction."xsd:string
http://purl.uniprot.org/citations/7566022http://purl.org/dc/terms/identifier"doi:10.1056/nejm199511163332003"xsd:string
http://purl.uniprot.org/citations/7566022http://purl.org/dc/terms/identifier"doi:10.1056/nejm199511163332003"xsd:string
http://purl.uniprot.org/citations/7566022http://purl.uniprot.org/core/author"Arai H."xsd:string
http://purl.uniprot.org/citations/7566022http://purl.uniprot.org/core/author"Arai H."xsd:string
http://purl.uniprot.org/citations/7566022http://purl.uniprot.org/core/author"Arita M."xsd:string
http://purl.uniprot.org/citations/7566022http://purl.uniprot.org/core/author"Arita M."xsd:string
http://purl.uniprot.org/citations/7566022http://purl.uniprot.org/core/author"Inoue K."xsd:string
http://purl.uniprot.org/citations/7566022http://purl.uniprot.org/core/author"Inoue K."xsd:string
http://purl.uniprot.org/citations/7566022http://purl.uniprot.org/core/author"Yamada N."xsd:string
http://purl.uniprot.org/citations/7566022http://purl.uniprot.org/core/author"Yamada N."xsd:string
http://purl.uniprot.org/citations/7566022http://purl.uniprot.org/core/author"Yokota T."xsd:string
http://purl.uniprot.org/citations/7566022http://purl.uniprot.org/core/author"Yokota T."xsd:string
http://purl.uniprot.org/citations/7566022http://purl.uniprot.org/core/author"Yazaki Y."xsd:string
http://purl.uniprot.org/citations/7566022http://purl.uniprot.org/core/author"Yazaki Y."xsd:string
http://purl.uniprot.org/citations/7566022http://purl.uniprot.org/core/author"Gotoda T."xsd:string
http://purl.uniprot.org/citations/7566022http://purl.uniprot.org/core/author"Gotoda T."xsd:string
http://purl.uniprot.org/citations/7566022http://purl.uniprot.org/core/author"Fukuo Y."xsd:string
http://purl.uniprot.org/citations/7566022http://purl.uniprot.org/core/author"Fukuo Y."xsd:string
http://purl.uniprot.org/citations/7566022http://purl.uniprot.org/core/date"1995"xsd:gYear
http://purl.uniprot.org/citations/7566022http://purl.uniprot.org/core/date"1995"xsd:gYear
http://purl.uniprot.org/citations/7566022http://purl.uniprot.org/core/name"N. Engl. J. Med."xsd:string
http://purl.uniprot.org/citations/7566022http://purl.uniprot.org/core/name"N. Engl. J. Med."xsd:string
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