Identification of new mutations in sterol 27-hydroxylase gene in Japanese patients with cerebrotendinous xanthomatosis (CTX).
Identification of new mutations in sterol 27-hydroxylase gene in Japanese patients with cerebrotendinous xanthomatosis (CTX).
复制标题
日本脑腱黄瘤病 (CTX) 患者甾醇 27-羟化酶基因新突变的鉴定。
作者：
K. S. Kim;S. Kubota;M. Kuriyama;J. Fujiyama;I. Björkhem;G. Eggertsen;Y. Seyama
脑腱黄瘤病(CTX)是一种遗传性的类固醇蓄积性疾病，与胆固醇和胆固醇类物质在各种组织中的积聚有关，尤其是肌腱和神经组织。导致CTX的生化缺陷是线粒体类固醇27-羟基酶缺乏，该酶氧化与胆汁酸形成有关的胆固醇侧链。日本CTX的流行率相对较高，在这里发现的病例比其他任何国家都多。在本研究中，在三名日本CTX患者和一名CTX杂合子中，描述了两个新的不同的点突变，该突变位于固醇27-羟基酶基因的血红素配体结合域。其中两个纯合子和杂合子受试者在密码子441[CGG(Arg)to CAG(Gln)]上有一个碱基A替代G。另一纯合子在第441位密码子[CGG(Arg)to TGG(Trp)]有C到T的转换。这两个不同的突变导致了StuI或HpaII酶的两个限制性片段长度多态性(RFLP)。我们还使用来自三名CTX患者、一名CTX杂合子和正常受试者的皮肤成纤维细胞来检测类固醇27-羟基酶活性。虽然两个纯合子受试者的酶活性水平检测不到，但一个纯合子受试者和一个杂合子受试者的酶活性水平降低，分别约为正常水平的1.4%和10%。结果提示，新发现的甾醇27-羟基酶基因点突变可能是日本CTX患者发生固醇27-羟基酶缺陷的原因。
Cerebrotendinous xanthomatosis (CTX) is a hereditary sterol storage disease associated with accumulation of cholesterol and cholestanol in various tissues, especially tendons and neural tissues. The biochemical defect that causes CTX is a deficiency of the mitochondrial sterol 27-hydroxylase which oxidizes the side chain of cholesterol in connection with formation of bile acids. Japan has a relatively high prevalence of CTX and more cases of the disease are found here than in any other country. In the present study two new different point mutations are described in the heme-ligand binding domain of the sterol 27-hydroxylase gene in three Japanese CTX patients and one CTX heterozygote. Two of the homozygotes as well as the heterozygote subject have a single base substitution of A for G at codon 441 [CGG (Arg) to CAG (Gln)]. Another homozygote has a transition of C to T at codon 441 [CGG (Arg) to TGG (Trp)]. These two different mutations result in two restriction fragment length polymorphisms (RFLPs) for the enzymes StuI or HpaII. We also assayed sterol 27-hydroxylase activity using skin fibroblasts derived from three CTX patients, one CTX heterozygote, and normal subjects. While two of the homozygous subjects have undetectable levels of the enzyme activity, one homozygous subject and one heterozygous subject have decreased levels of the enzyme activity, about 1.4% and 10% of normal, respectively. The results suggest that the newly identified point mutations in the sterol 27-hydroxylase gene could account for the sterol 27-hydroxylase deficiency in the Japanese CTX patients.
影响因子：
158.5
作者：
BERGINER, VM;SALEN, G;SHEFER, S
通讯作者：
SHEFER, S
DOI：
--
发表时间：
1991-04
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
J. Cali;C. Hsieh;Chih-Lin Hsieh;U. Francke;U. Francke;D. Russell
通讯作者：
J. Cali;C. Hsieh;Chih-Lin Hsieh;U. Francke;U. Francke;D. Russell
证明人皮肤成纤维细胞中 C27-类固醇的 26-羟基化，以及脑腱黄瘤病中缺乏这种活性。
DOI：
10.1172/jci112633
发表时间：
1986
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
Skrede,S;Bjorkhem,I;Kvittingen,EA;Buchmann,MS;Lie,SO;East,C;Grundy,S
通讯作者：
Grundy,S