title: A novel mutation in the cytochrome P450(27) (CYP27) gene caused cerebrotendinous xanthomatosis in a Japanese family.
abstract: Cerebrotendinous xanthomatosis (CTX) is an autosomal recessive lipid storage disease caused by mutations in the cytochrome P450(27) (CYP27) gene. This disease is characterized by the accumulation of a bile alcohol, cholestanol, in diverse tissues. Accumulation in the central nervous system leads to neurological dysfunction including dementia, spinal cord paresis, and cerebellar ataxia. Accumulation in other tissues causes tendon xanthomas, premature atherosclerosis, and cataracts. In a Japanese family with CTX, we identified two points mutations in the CYP27 gene at different sites. One is a novel transversion, which substitutes G for C at Pro 368 (CCC) to Arg (CGC). The other is a transition, which substitutes A for G at Arg441 (CGG) to Gln (CAG), this being the same mutation that Kim et al. reported (1994. J. Lipid Res. 35: 1031 - 1039). Allele-specific polymerase chain reaction analysis indicated that the father and mother of this family, who themselves had no clinical manifestations of CTX, had the former and latter mutations heterozygously, respectively. On the other hand, the patients each had both mutations heterozygously. These results are highly suggestive, but not conclusive, that the newly identified transversion in the CYP27 gene accounts for the sterol 27-hydroxylase (EC 1.14.13.15) deficiency in these patients.
authors.affiliation: Department of Biochemistry, Kagawa Medical School, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Okuyama
authors.forename: S
authors.initials: S
authors.lastname: Tomita
authors.forename: H
authors.initials: H
authors.lastname: Takeuchi
authors.forename: Y
authors.initials: Y
authors.lastname: Ichikawa
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D053493:Cholestanetriol 26-Monooxygenase; D004083:Cholestanol / Q000097:blood; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000172:deficiency / Q000235:genetics*; D005091:Exons; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D007564:Japan; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D017421:Sequence Analysis; D013250:Steroid Hydroxylases / Q000737:chemistry / Q000172:deficiency / Q000235:genetics*; D019294:Xanthomatosis, Cerebrotendinous / Q000201:enzymology / Q000235:genetics*
chemical_list: D004083:Cholestanol; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; C506831:CYP27A1 protein, human; D053493:Cholestanetriol 26-Monooxygenase