CBS GENE IN HOMOCYSTINURIA AND ARTERIOSCLEROSIS

产品说明： 父母补助金的目的是阐明遗传、生化和 代谢紊乱导致精神 （Stephen Goodman，P.I.）。申请人（Jan P. Kraus，Ph.D.） 我们是这个项目的项目负责人，并开发了这个 申请与Viktor Kozich，M.D.，博士于查理 捷克共和国布拉格的大学。申请人建议确定 胱硫醚B合酶基因表达改变的机制 (CBS)经典同型胱氨酸尿症中的基因（与父母补助金有关）， 在患有冠状动脉/外周动脉疾病的患者中（同型半胱氨酸 代谢和动脉粥样硬化），其中轻度高同型半胱氨酸血症是 礼物调查的目的是确定分子 可能与有效诊断相关的CBS基因相关事件 和治疗这些疾病。申请人侧重于以下方面的作用： 一个常见的（5-9%的人群）多态性（844 ins 68 bp等位基因在 CBS基因）与同型胱氨酸尿症的发生率有关， 该等位基因在诱导一种常见突变（1278 T）中的作用， 解释疾病的发生率和等位基因突变对 正常CBSmRNA在培养的成纤维细胞中的稳定状态。一个广泛 CBS基因突变的分析将从血液中进行评估 从国外收集的同型胱氨酸尿症患者的样本， 在不同的人群中分布不同。最后 申请人建议研究如何在调控部分的突变， CBS基因可能导致CBS表达降低，导致异常的 同型半胱氨酸代谢

DESCRIPTION: The parent grant has its aims the elucidation of genetic, biochemical and pathogenetic aspects of metabolic disorders resulting in mental retardation (Stephen Goodman, P.I.). The applicant (Jan P. Kraus, Ph.D.) us a Project Leader in this program project grant and has developed this application to collaborate with Viktor Kozich, M.D., Ph.D. from Charles University in Prague, Czech Republic. The applicant proposes to determine the mechanisms of altered gene expression of the cystathionine b-synthase (CBS) gene in classical Homocystinuria (related to the Parent Grant) and also in patients with coronary/peripheral arterial disease (Homocysteine metabolism and atherosclerosis) in whom a mild hyperhomocystinemia is present. The purpose of the investigation is to define the molecular events related to the CBS gene that may be relevant to efficient diagnosis and treatment of these disorders. The applicant is focusing on the role of a frequent (5-9% of the population) polymorphism (844ins68bp allele in the CBS gene) with respect to the incidence of homocystinuria, the possible role of this allele in inducing a common mutation(1278T) that may also explain the incidence of disease and the impact of the allele mutation on the steady state of normal CBSmRNA in cultured fibroblasts. An extensive analysis of the mutations in the CBS gene will be evaluated from blood samples of patients with homocystinuria from abroad ad mutations have been shown to be differently distributed in various populations. Finally the applicant proposes to study how the mutations in regulatory portions of the CBS gene may have caused the low CBS expression leading to abnormal homocysteine metabolism.