title: Novel homozygous and compound heterozygous mutations of sterol 27-hydroxylase gene (CYP27) cause cerebrotendinous xanthomatosis in three Japanese patients from two unrelated families.
abstract: The autosomal recessively inherited cholesterol metabolic disease, cerebrotendinous xanthomatosis (CTX), is caused by mutations in the sterol 27-hydroxylase gene. Three Japanese CTX patients from two unrelated families were studied genetically. By DNA sequence analysis a novel mutation of A for G substitution at amino acid position 372 (CGG 372Arg to CAG 372Gln) was identified in one of the CTX families. The mutation was also found in two patients from the other family, with a compound heterozygous pattern of A for G substitution at amino acid position 441 (CGG 441Arg to CAG 441Gln). The latter mutation was the same as previously reported by our group (J. Lipid Res. 1994. 35: 1031-1039). As the two mutations changed the restriction enzyme sites, rapid screening methods were developed for the detection of the carriers. Transfection of the two mutant cDNAs into COS cells resulted in markedly reduced sterol 27-hydroxylase activity. These results indicate that the two mutations are responsible for the deficiency of the sterol 27-hydroxylase activity in these patients. The features of mutations identified till now in Japanese CTX patients are also reviewed.
authors.affiliation: Department of Physiological Chemistry and Nutrition, Faculty of Medicine, Japan.
authors.forename: W
authors.initials: W
authors.lastname: Chen
authors.forename: S
authors.initials: S
authors.lastname: Kubota
authors.forename: K S
authors.initials: KS
authors.lastname: Kim
authors.forename: J
authors.initials: J
authors.lastname: Cheng
authors.forename: M
authors.initials: M
authors.lastname: Kuriyama
authors.forename: G
authors.initials: G
authors.lastname: Eggertsen
authors.forename: I
authors.initials: I
authors.lastname: Björkhem
authors.forename: Y
authors.initials: Y
authors.lastname: Seyama
mesh_terms: D053493:Cholestanetriol 26-Monooxygenase; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007564:Japan; D008297:Male; D009154:Mutation; D010375:Pedigree; D013250:Steroid Hydroxylases / Q000235:genetics*; D019294:Xanthomatosis, Cerebrotendinous / Q000235:genetics*
chemical_list: D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; C506831:CYP27A1 protein, human; D053493:Cholestanetriol 26-Monooxygenase