A point mutation in the bile acid biosynthetic enzyme sterol 27- hydroxylase in a family with cerebrotendinous xanthomatosis

N. Nakashima, Y. Sakai, H. Sakai, T. Yanase, M. Haji, F. Umeda, S. Koga, T. Hoshita, H. Nawata

研究成果: Contribution to journalArticle査読

30 被引用数 (Scopus)

抄録

Cerebrotendinous xanthomatosis (CTX) is a rare familial disorder characterized by progressive neurological dysfunction, atherosclerosis, and xanthomas with sterol-storage in the nervous system, vessels, and tendons. Increased serum cholestanol, derived from intermediates of cholesterol catabolism, may possibly be a major cause of the disease. An examination was made of the cDNA encoding cytochrome P450 sterol 27-hydroxylase (CYP27) in hepatic mitochondria, considered a defective enzyme inducing CTX, in a Japanese housewife afflicted with CTX and her family. The proposita and one of her brothers, who also had CTX symptoms and hypercholestanolemia, were found to be homozygotic, carrying a point mutation in the CYP27 gene at Arg104 (CGG) to Trp104 (TGG). The mutant position has a 100% conserved positive charge in all known vertebrate cytochrome P450s and even in bacterial cytochrome P450cam. The mother of the proposita and another brother were both free of CTX symptoms and were heterozygotic for the mutation, although their plasma cholestanol increased moderately. An increase in plasma cholestanol alone would, thus, not appear to be a direct cause of sterol storage in CTX, while CTX is strongly suggested to be caused by defects in both alleles of the CYP27 gene.

本文言語英語
ページ(範囲)663-668
ページ数6
ジャーナルJournal of Lipid Research
35
4
出版ステータス出版済み - 1994

All Science Journal Classification (ASJC) codes

  • 生化学
  • 内分泌学
  • 細胞生物学

フィンガープリント

「A point mutation in the bile acid biosynthetic enzyme sterol 27- hydroxylase in a family with cerebrotendinous xanthomatosis」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル