NOVEL TYPES OF FAMILIAL DIABETES INSIPIDUS

本研究的目的是确定以前未描述类型的家族性尿崩症（FDI）的表型和遗传基础。 所有知情同意的似乎存在新型FDI分离的患者将被CRC接受一系列检测，以确定FDI的存在、不存在、原因、自然史、临床伴随因素和干扰模式。 这些评价将包括全面的病史和体格检查以及基础液体摄入量和尿排出量、垂体后叶和前叶功能、姿势血流动力学、交感神经和肾素系统的活性、垂体和下丘脑的MRI以及二尖瓣和主动脉瓣的超声心动图的标准临床测量。 此外，将通过检测表型与已知遗传基因座和/或多态性VTRS（可变串联重复序列）标记（已知位于整个人类基因组中的紧密间隔）的其他疾病的连锁，对导致FDI的遗传突变进行定位。 这些信息将有助于提高表型分析的准确性，并阐明这种和其它类型FDI的发病机理。它也可能有助于了解其他遗传性中枢神经功能障碍的遗传基础。

The objective of this study is to define the phenotype and genetic basis of previously undescribed types of familial diabetes insipidus (FDI). All consenting members of kindreds in which novel types of FDI appear to be segregating will be admitted to the CRC for a series of tests to determine the presence, absence, cause, natural history, clinical concomitants and mode of interitance of the FDI. These evaluation will include a thorough history and physical examination as well as standard clinical measurements of basal fluid intake and urine output, posterior and anterior pituitary function, postural hemodynamics, the activity of the sympathetic and renin systems, MRI of the pituitary and hypothalamus and echocardiograms of the mitral and aortic valves. In addition, the genetic mutation responsible for the FDI will be mapped by testing for linkage of the phenotype to other diseases of known genetic locus and/or polymorphic VTRS (variable tandem repeat sequence) markers known to be located at close intervals throughout the human genome. this information will serve to improve the accuracy of phenotyping and clarify the pathogenesis of this and other types of FDI. It may also prove useful in understanding the genetic basis of other inherited disabilities of central nervous function.