UCRC SPECIAL CASE STUDY PROTOCOL

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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.