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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 hHis01Gln 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 ug per milliliter[17.4+/-5.1 vs.23.4+/-6.5 umol per liter];P=0.002).Alpha-tocopherol-transfer protein is a determinant of serum vitamin E concentrations.An abnormality in this protein is a cause of spinocerebellar dysfunction. |
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