HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kim, K. S. Articles by Seyama, Y. Search for Related Content PubMed PubMed Citation Articles by Kim, K. S. Articles by Seyama, Y. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol 35, 1031-1039, Copyright © 1994 by Lipid Research, Inc.

ARTICLES

Identification of new mutations in sterol 27-hydroxylase gene in Japanese patients with cerebrotendinous xanthomatosis (CTX)

KS Kim, S Kubota, M Kuriyama, J Fujiyama, I Bjorkhem, G Eggertsen and Y Seyama
Department of Physiological Chemistry and Nutrition, Faculty of Medicine, University of Tokyo, Japan.

Cerebrotendinous xanthomatosis (CTX) is a hereditary sterol storage disease associated with accumulation of cholesterol and cholestanol in various tissues, especially tendons and neural tissues. 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. Japan has a relatively high prevalence of CTX and more cases of the disease are found here than in any other country. In the present study two new different point mutations are described 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 StuI or HpaII. We also assayed sterol 27-hydroxylase activity using skin fibroblasts derived from three CTX patients, one CTX heterozygote, and normal subjects. While two of the homozygous subjects have undetectable levels of the enzyme activity, one homozygous subject and one heterozygous subject have decreased levels of the enzyme activity, about 1.4% and 10% of normal, respectively. The results suggest that the newly identified point mutations in the sterol 27- hydroxylase gene could account for the sterol 27-hydroxylase deficiency in the Japanese CTX patients.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				A. K. Bhattacharyya, D. S. Lin, and W. E. Connor Cholestanol metabolism in patients with cerebrotendinous xanthomatosis: absorption, turnover, and tissue deposition J. Lipid Res., January 1, 2007; 48(1): 185 - 192. [Abstract] [Full Text] [PDF]

				A. Honda, G. Salen, Y. Matsuzaki, A. K. Batta, G. Xu, T. Hirayama, G. S. Tint, M. Doy, and S. Shefer Disrupted coordinate regulation of farnesoid X receptor target genes in a patient with cerebrotendinous xanthomatosis J. Lipid Res., February 1, 2005; 46(2): 287 - 296. [Abstract] [Full Text] [PDF]

				Y. Ota, T.-A. Eto, S.-I. Tanaka, H. Sueta, H. Shiotsuki, Y. Maeda, M. Une, and K. Chijiiwa Assay method for mitochondrial sterol 27-hydroxylase with 7{alpha}-hydroxy-4-cholesten-3-one as a substrate in the rat liver J. Lipid Res., December 1, 2003; 44(12): 2400 - 2405. [Abstract] [Full Text] [PDF]

				M.-H. Lee, S. Hazard, J. D. Carpten, S. Yi, J. Cohen, G. T. Gerhardt, G. Salen, and S. B. Patel Fine-mapping, mutation analyses, and structural mapping of cerebrotendinous xanthomatosis in U.S. pedigrees J. Lipid Res., February 1, 2001; 42(2): 159 - 169. [Abstract] [Full Text]

				A. Honda, G. Salen, Y. Matsuzaki, A. K. Batta, G. Xu, E. Leitersdorf, G. S. Tint, S. K. Erickson, N. Tanaka, and S. Shefer Differences in hepatic levels of intermediates in bile acid biosynthesis between Cyp27-/- mice and CTX J. Lipid Res., February 1, 2001; 42(2): 291 - 300. [Abstract] [Full Text]

				A. Verrips, L. H. Hoefsloot, G. C. H. Steenbergen, J. P. Theelen, R. A. Wevers, F. J. M. Gabreels, B. G. M. van Engelen, and L. P. W. J. van den Heuvel Clinical and molecular genetic characteristics of patients with cerebrotendinous xanthomatosis Brain, May 1, 2000; 123(5): 908 - 919. [Abstract] [Full Text] [PDF]

				G. J. Schroepfer Jr. Oxysterols: Modulators of Cholesterol Metabolism and Other Processes Physiol Rev, January 1, 2000; 80(1): 361 - 554. [Abstract] [Full Text] [PDF]

				K Shiga, R Fukuyama, S Kimura, K Nakajima, and S Fushiki Mutation of the sterol 27-hydroxylase gene (CYP27) results in truncation of mRNA expressed in leucocytes in a Japanese family with cerebrotendinous xanthomatosis J. Neurol. Neurosurg. Psychiatry, November 1, 1999; 67(5): 675 - 677. [Abstract] [Full Text]

				N. Wakamatsu, M. Hayashi, H. Kawai, H. Kondo, Y. Gotoda, Y. Nishida, R. Kondo, S. Tsuji, and T. Matsumoto Mutations producing premature termination of translation and an amino acid substitution in the sterol 27-hydroxylase gene cause cerebrotendinous xanthomatosis associated with parkinsonism J. Neurol. Neurosurg. Psychiatry, August 1, 1999; 67(2): 195 - 198. [Abstract] [Full Text] [PDF]

				D.-Y. Tai, J.-P. Pan, and G.-J. Lee-Chen Identification and haplotype analysis of apolipoprotein B-100 Arg3500->Trp mutation in hyperlipidemic Chinese Clin. Chem., August 1, 1998; 44(8): 1659 - 1665. [Abstract] [Full Text] [PDF]

				H. Rosen, A. Reshef, N. Maeda, A. Lippoldt, S. Shpizen, L. Triger, G. Eggertsen, I. Bjorkhem, and E. Leitersdorf Markedly Reduced Bile Acid Synthesis but Maintained Levels of Cholesterol and Vitamin D Metabolites in Mice with Disrupted Sterol 27-Hydroxylase Gene J. Biol. Chem., June 12, 1998; 273(24): 14805 - 14812. [Abstract] [Full Text] [PDF]

				W. Chen, S. Kubota, and Y. Seyama Alternative pre-mRNA splicing of the sterol 27-hydroxylase gene (CYP 27) caused by a G to A mutation at the last nucleotide of exon 6 in a patient with cerebrotendinous xanthomatosis (CTX) J. Lipid Res., March 1, 1998; 39(3): 509 - 517. [Abstract] [Full Text]

				R. S. Kushwaha, B. Guntupalli, K. S. Rice, K. D. Carey, and H. C. McGill Jr Effect of Dietary Cholesterol and Fat on the Expression of Hepatic Sterol 27-Hydroxylase and Other Hepatic Cholesterol-Responsive Genes in Baboons (Papio Species) Arterioscler. Thromb. Vasc. Biol., September 1, 1995; 15(9): 1404 - 1411. [Abstract] [Full Text]

				D. Gaffney, J. M. Reid, I. M. Cameron, K. Vass, M. J. Caslake, J. Shepherd, and C. J. Packard Independent Mutations at Codon 3500 of the Apolipoprotein B Gene Are Associated With Hyperlipidemia Arterioscler. Thromb. Vasc. Biol., August 1, 1995; 15(8): 1025 - 1029. [Abstract] [Full Text]

				A. Honda, G. Salen, Y. Matsuzaki, A. K. Batta, G. Xu, E. Leitersdorf, G. S. Tint, S. K. Erickson, N. Tanaka, and S. Shefer Side Chain Hydroxylations in Bile Acid Biosynthesis Catalyzed by CYP3A Are Markedly Up-regulated in Cyp27-/- Mice but Not in Cerebrotendinous Xanthomatosis J. Biol. Chem., September 7, 2001; 276(37): 34579 - 34585. [Abstract] [Full Text] [PDF]