UCRC SPECIAL CASE STUDY PROTOCOL

本协议的目的是提供UCRC评估机制， 更详细地描述了似乎具有独特的 疾病进程，已确定疾病的独特子集，独特的 对药物治疗的反应等。有时，UCRC被称为 教师关于病人或家庭谁似乎是独一无二的。 作为第一步，希望在一个实验室中研究这些患者。 受控环境，如UCRC提供的严格 控制饮食，定量收集尿液和粪便， 在常规或常规检查中进行各种测定的血液采样 特殊实验室 有时候，这样的病人可以“适应”到 已经批准的协议，但如果不能，可以输入 这个特殊的案例研究方案 通过该方案，初步 可以获得信息，如果确实出现患者 具有独特的特点，值得进一步研究，数据 生成的数据可用于开发后续协议。 一名调查员 希望使用本方案的患者必须向UCRC和IRB提交 患者独特特征的简要书面描述， 建议使用UCRC的理由和程序， 执行。 这必须附有同意书。 的批准 UCRC项目总监和IRB必须在 可以进行研究。预计该协议将在 在任何一年内，仅适用于少数患者或家庭。 今年，该协议被Dianna Milewicz博士使用， 医学遗传学部。一个男人引起了她的注意 他有终身出血性疾病和异常凝血研究。 的 患者的疾病不符合任何公认的凝血异常。 对该患者及其家人的实验室研究得出了以下假设 这种独特的出血性疾病是由于一种新的抗凝血酶III基因 （ATIII）突变，导致抗凝血酶III具有组成性活性 在没有肝素结合的情况下，即，功能获得性突变 导致抗凝血酶III活性过高 无其他功能增益 已经描述了ATIII中的突变。 这一假设正在接受检验 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.