CBS GENE IN HOMOCYSTINURIA AND ARTERIOSCLEROSIS

说明： 家长基金的目的是阐明遗传、生物化学和 代谢紊乱导致精神疾病的病因学方面 迟缓(史蒂芬·古德曼，P.I.)申请人(Jan P.Kraus，Ph.D.) 美国是该计划的项目负责人，项目赠款，并开发了 申请与来自查尔斯的医学博士Viktor Kozich合作 捷克布拉格大学。申请人提议确定 胱硫醚b-合酶基因表达改变的机制 经典同型半胱氨酸尿症(CBS)基因(与父母Grant有关)和 冠状动脉/外周动脉疾病患者(同型半胱氨酸 代谢和动脉粥样硬化)，其中有轻度高同型半胱氨酸血症 现在时。这项研究的目的是定义分子 可能与有效诊断相关的与CBS基因相关的事件 以及对这些疾病的治疗。申请者关注的是 人群中常见的(5%-9%)多态(844in68bp等位基因) CBS基因)关于同型半胱氨酸尿症的发生率，可能 该等位基因在诱发常见突变(1278T)中的作用 解释疾病的发病率和等位基因突变对 培养成纤维细胞中正常CBSmRNA的稳定状态。广泛的 CBS基因突变的分析将从血液中进行评估 来自国外的同型半胱氨酸尿症患者的样本已经突变 在不同的人群中表现出不同的分布。最后是 申请者建议研究基因调控部分的突变是如何 CBS基因可能是导致CBS低表达导致异常的原因 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.