UCRC SPECIAL CASE STUDY PROTOCOL

该议定书的目的是提供对UCRC进行评估的机制 更详细地说，患者的特征似乎是独一无二的 疾病进程，已识别疾病的唯一子集，唯一 对药物治疗的反应等。偶尔，UCRC会被一名 关于看似独一无二的病人或家属的教员。 作为第一步，最好对这类患者进行研究。 受控制的环境，如UCRC提供的具有严格 控制饮食，定量收集尿液和粪便，以及 用于各种常规或非常规测定的血液样本 特殊实验室。偶尔，这样的病人可能会“适应”到 已经批准的协议，但如果他们不能，他们可以进入 这个特殊的案例研究方案。通过这个协议，初步 可以获得的信息，如果确实出现了病人 具有独特的特点和值得进一步研究的数据 生成的协议可用于开发后续协议。一名调查员 希望使用该议定书必须向UCRC和IRB提交一份 对患者独特特征的简短书面描述，并附有 建议使用城市轨道交通中心的理由和程序如下 已执行。此表格必须附有同意书。批准来自 UCRC计划主任和IRB必须在 可以进行研究。预计该协议将是 仅适用于任何一年内的少数患者或家属。 今年，世界卫生组织总干事戴安娜·米列维奇博士使用了这一方案 医学遗传学分部。一个男人引起了她的注意，因为 他有终生出血性疾病和异常凝血研究。这个 患者的紊乱不符合任何公认的凝血异常。 对这名患者及其家人的实验室研究导致了这一假说 这种独特的出血性疾病是由一种新的抗凝血酶III基因引起的 (ATIII)导致抗凝血酶III具有结构性活性的突变 在没有肝素结合的情况下，即功能获得突变 导致过度活性的抗凝血酶III。没有其他功能增强 ATIII的突变已经被描述。这一假说正在接受检验。 通过使用受影响家庭成员的DNA对ATIII基因进行测序。

The aim of this protocol is to provide the mechanism on the UCRC to assess in more detail the characteristics of patients who appear to have unique disease precesses, unique subsets of an already identified disease, unique responses to drug therapy, etc. Occasionally, the UCRC is called by a faculty member concerning a patient or family who appears to be unique. As a first step, it would be desirable to study such patients in a controlled environment such as that offered by the UCRC with a rigidly controlled diet, quantitative collection of urine and feces, and serial sampling of blood for a variety of determinations in either routine or special laboratories. Occasionally such patients can be "fit" into already approved protocols, but if they cannot, they can be entered into this special case study protocol. Through this protocol, preliminary information can be gained, and if it does indeed appear that the patient has unique characteristics and warrants further studies, the data generated can be used to develop subsequent protocols. An investigator wishing to utilize this protocol must submit to the UCRC and to the IRB a brief written description of the patient's unique characteristics, with a justification of the proposed use of the UCRC and procedures to be performed. This must be accompanied by a consent form. Approval from both the UCRC Program Director and the IRB must be obtained before the study can be conducted. It is anticipated that this protocol will be applicable to only a few patients or families within any given year. This year, the protocol was utilized by Dr. Dianna Milewicz, chief of the division of Medical Genetics. A man was brought to her attention because he has a lifelong bleeding disorder and abnormal coagulation studies. The patient's disorder did not fit any recognized coagulation abnormalities. Laboratory studies of this patient and his family led to the hypothesis that the unique bleeding disorder is due to a novel antithrombin III gene (ATIII) mutation that causes antithrombin III to be constitutively active in the absence of heparin binding, i.e., a gain-of-function mutation leading to an overly active antithrombin III. No other gain-of-function mutations in ATIII have been described. This hypothesis is being tested by sequencing the ATIII gene using DNA from affected family members.