1993 Fiscal Year Final Research Report Summary
Genetic diagnosis of cerebrotendinous xanthomatosis
| Project/Area Number |
04454167
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Pathological medical chemistry
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| Research Institution | University of Tokyo |
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Principal Investigator |
SEYAMA Yousuke Univ.Tokyo, Facult.Med., Prof., 医学部・(医), 教授 (90010082)
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| Co-Investigator(Kenkyū-buntansha) |
KURIYAMA Masaru Kagoshima Univ.Facult.Med.Assoc.Prof., 医学部, 助教授 (80107870)
KANO Kazutaka Univ.Tokyo, Facult.Med., Associate, 医学部・(医), 助手 (70111507)
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| Project Period (FY) |
1992 – 1993
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| Keywords | Cerebrotendinous Xanthomatosis / CTX / Genetic Diagnosis / Sterol 27-Hydroxylase / RFLP |
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| Research Abstract |
Cerebrotendinous xanthomatosis (CTX) is a hereditary sterol storage disease. The biochemical defect that causes CTX is a deficiency of the mitochondrial sterol 27-hydroxylase which oxidizes the side chain of cholesterol in connection with formation of bile acids. In the present study two new different point mutations are found in the heme-ligand binding domain of the sterol 27-hydroxylase gene in three Japanese CTX patients and one CTX heterozygote. Two of the homozygotes as well as the heterozygote subject have a single base substitution of A for G at codon 441 [CGG(Arg) to CAG(Gln)]. Another homozygote has a transition of C to T at codon 441 [CGG(Arg) to TGG(Trp)]. These two different mutations result in two restriction fragment length polymorphisms (RFLPs) for the enzymes Stu I or Hpa II.We also assayd sterol 27-hydroxylase activity using skin fibroblasts from these patients. While two of the homozygous subjects have undetectable levels of the enzyme activity, one homozygous and heterozygous subjects have decreased levels of the enzyme activity. These results suggest that the newly identified point mutations in the sterol 27-hydroxylase gene could account for the sterol 270-hydroxylase deficiency in the Japanese CTX patients.
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