Genetic analysis of a Japanese cerebrotendinous xanthomatosis family: identification of a novel mutation in the adrenodoxin binding region of the CYP 27 gene

Biochim Biophys Acta. 1996 Nov 15;1317(2):119-26. doi: 10.1016/s0925-4439(96)00043-9.


Cerebrotendinous xanthomatosis (CTX), an autosomal recessive lipid-storage hereditary disorder, is caused by mutations in the sterol 27-hydroxylase gene (CYP 27). A 24-year-old female Japanese CTX patient and her parents were studied for a CYP 27 mutation. Multiple xanthomas were the main complaint of the patient and plasma cholestanol level was markedly elevated. Sterol analysis of a xanthoma biopsy confirmed cholesterol and cholestanol deposition, and the cholestanol accounted for 8.1% of the total sterols. Sterol 27-hydroxylase activity in fibroblasts derived from the patient was undetectable, while the activities in fibroblasts from her mother and father were 54% and 41% of the normal level, respectively. Direct sequence analysis showed a missense mutation of A for G substitution in the CYP 27 gene at codon 362 (CGT 362Arg to CAT 362His) with a homozygous pattern in the patient, and a heterozygous pattern in the parents. The mutation, which eliminates a normal HgaI endonuclease site at position 1195 of the cDNA and is located at the adrenodoxin binding region of the gene, is most probably responsible for the decreased sterol 27-hydroxylase activity in this Japanese CTX family. The combined data strongly support that the primary enzymatic defect in CTX is the disruption of sterol 27-hydroxylase and that the disease is inherited in an autosomal recessive trait.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenodoxin / metabolism
  • Binding Sites
  • Cholestanetriol 26-Monooxygenase
  • Cytochrome P-450 Enzyme System / genetics*
  • Female
  • Fibroblasts / enzymology
  • Genes, Recessive
  • Humans
  • Japan / ethnology
  • Point Mutation
  • Polymorphism, Restriction Fragment Length
  • Polymorphism, Single-Stranded Conformational
  • Steroid Hydroxylases / genetics*
  • Xanthomatosis, Cerebrotendinous / genetics*


  • Adrenodoxin
  • Cytochrome P-450 Enzyme System
  • Steroid Hydroxylases
  • CYP27A1 protein, human
  • Cholestanetriol 26-Monooxygenase