Mutations in the bile acid biosynthetic enzyme sterol 27-hydroxylase underlie cerebrotendinous xanthomatosis

James J. Cali, Chih Lin Hsieh, Uta Francke, David W. Russell

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Abstract

The sterol storage disorder cerebrotendinous xanthomatosis (CTX) is characterized by abnormal deposition of cholesterol and cholestanol in multiple tissues. Deposition in the central nervous system leads to neurological dysfunction marked by dementia, spinal cord paresis, and cerebellar ataxia. Deposition in other tissues causes tendon xanthomas, premature atherosclerosis, and cataracts. In two unrelated patients with CTX, we have identified different point mutations in the gene (CYP27) encoding sterol 27-hydroxylase, a key enzyme in the bile acid biosynthesis pathway. Transfection of mutant cDNAs into cultured cells results in the synthesis of immunoreactive sterol 27-hydroxylase protein with greatly diminished enzyme activity. We have localized the CYP27 gene to the q33-qter interval of human chromosome 2, and to mouse chromosome 1, in agreement with the autosomal recessive inheritance pattern of CTX. These findings underscore the essential role played by sterols in the central nervous system and suggest that mutations in other sterol metabolizing enzymes may contribute to diseases with neurological manifestations.

Original languageEnglish (US)
Pages (from-to)7779-7783
Number of pages5
JournalJournal of Biological Chemistry
Volume266
Issue number12
StatePublished - Apr 25 1991

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Cholestanetriol 26-Monooxygenase
Cerebrotendinous Xanthomatosis
Sterols
Bile Acids and Salts
Neurology
Chromosomes
Mutation
Enzymes
Central Nervous System
Cholestanol
Tissue
Xanthomatosis
Inheritance Patterns
Cerebellar Ataxia
Gene encoding
Chromosomes, Human, Pair 2
Chromosomes, Human, Pair 1
Biosynthesis
Tendons
Enzyme activity

ASJC Scopus subject areas

  • Biochemistry

Cite this

Mutations in the bile acid biosynthetic enzyme sterol 27-hydroxylase underlie cerebrotendinous xanthomatosis. / Cali, James J.; Hsieh, Chih Lin; Francke, Uta; Russell, David W.

In: Journal of Biological Chemistry, Vol. 266, No. 12, 25.04.1991, p. 7779-7783.

Research output: Contribution to journalArticle

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