Department of Neurology, University of Technology Dresden, University Clinic, Fetscherstr 74, 01307 Dresden, Germany.
Orphanet J Rare Dis. 2010 Oct 6;5:27. doi: 10.1186/1750-1172-5-27.
Mutations of the gene encoding the mitochondrial enzyme sterol 27-hydroxylase (CYP27A1 gene) cause defects in the cholesterol pathway to bile acids that lead to the storage of cholestanol and cholesterol in tendons, lenses and the central nervous system. This disorder is the cause of a clinical syndrome known as cerebrotendinous xanthomatosis (CTX). Since 1991 several mutations of the CYP27A1 gene have been reported. We diagnosed the clinical features of CTX in a caucasian woman. Serum levels of cholestanol and 7α-hydroxycholesterol were elevated and the concentration of 27-hydroxycholesterol was reduced. Bile alcohols in the urine and faeces were increased. The analysis of the CYP27A1 gene showed that the patient was a compound heterozygote carrying two mutations both located in exon 8. One mutation is a novel four nucleotide deletion (c.1330-1333delTTCC) that results in a frameshift and the occurrence of a premature stop codon leading to the formation of a truncated protein of 448 amino acids. The other mutation, previously reported, is a C - > T transition (c. c.1381C > T) that converts the glutamine codon at position 461 into a termination codon (p.Q461X). These truncated proteins are expected to have no biological function being devoid of the cysteine residue at position 476 of the normal enzyme that is crucial for heme binding and enzyme activity.
编码线粒体酶甾醇 27-羟化酶（CYP27A1 基因）的基因突变导致胆固醇向胆汁酸的途径出现缺陷，从而导致胆固醇醇和胆固醇在肌腱、晶状体和中枢神经系统中蓄积。这种疾病是导致一种称为脑腱黄瘤病（CTX）的临床综合征的原因。自 1991 年以来，已经报道了 CYP27A1 基因的几种突变。我们诊断了一位白人妇女的 CTX 临床特征。血清中胆固醇醇和 7α-羟胆固醇水平升高，27-羟胆固醇浓度降低。尿液和粪便中的胆汁醇增加。CYP27A1 基因分析表明，患者是携带两个突变的复合杂合子，这两个突变均位于外显子 8 中。一个突变是一个新的四核苷酸缺失（c.1330-1333delTTCC），导致移码和过早的终止密码子的发生，导致形成 448 个氨基酸的截断蛋白。另一个突变是先前报道的 C - > T 转换（c. c.1381C > T），将 461 位的谷氨酰胺密码子转换为终止密码子（p.Q461X）。这些截断的蛋白预计没有生物学功能，因为正常酶中位于第 476 位的半胱氨酸残基缺失，该残基对于血红素结合和酶活性至关重要。
