HYPO- AND HYPERADRENAL STATES - SALT DEPRIVATION STUDY

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 大量的遗传性和获得性疾病会影响肾上腺皮质的功能，导致肾上腺皮质功能降低(低)或高(高)。我们的团队致力于阐明激素生成障碍的生化缺陷和分子遗传学基础，主要是先天性肾上腺增生症。在过去的50年里，我们广泛研究了这些疾病的临床、激素和分子遗传学基础，确定了导致疾病的类固醇合成途径中的缺陷，并建立了针对酶缺陷的治疗方法。在导致疾病的基因突变已经确定的情况下(例如21-羟基酶缺乏，占所有CAH病例的90%-95%)并且疾病机制已知的情况下，这可能是直接的；然而，在尚未确定决定基因并且疾病机制仍然未知的情况下，这可能特别困难。因此，下面的方案概述了我们能够用来描述罕见类固醇生成酶缺陷患者及其家庭成员的不同临床谱系的方法。 与CAH相关的假设： 1.在盐耗、单纯性阳萎和因21-羟基酶缺乏所致的非经典型先天性肾上腺增生症(CAH)患者中，基因分型可预测表型。 2.有一些基因型与表型不一致的例子，特别是关于盐耗的显著特征，值得调查。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. A large number of inherited and acquired disorders can affect the function of the adrenal cortex, causing either reduced (hypo) or increased (hyper) adrenocortical function. Our team has focused on elucidating the biochemical defects and the molecular genetic basis of disorders of steroidogenesis, primarily in Congenital Adrenal Hyperplasia. Over the past 50 years, we have studied extensively the clinical, hormonal and molecular genetic basis of these disorders, identifying the defect within the steroid synthesis pathway which causes the disease and establishing a treatment which specifically targets the enzyme defect. This can be straightforward in cases where the genetic mutations causing a disease have been characterized (eg 21-hydroxylase deficiency, accounting for 90-95% of all CAH cases) and the mechanism of disease is known; however, this can be particularly difficult in cases where the determinant gene has not yet been identified and the mechanism of disease remains unknown. Therefore the following protocol outlines the means by which we are able to characterize the diverse clinical spectra of patients with rare steroidogenesic enzyme defects and their family members. Hypothesis related to CAH: 1. Genotype predicts phenotype in patients with salt wasting, simple virilizing, and the non-classical forms of congenital adrenal hyperplasia (CAH) owing to 21-hydroxylase deficiency. 2. There are examples of non-concordance of genotype to phenotype, particularly with regard to the salient feature of salt-wasting, which merit investigation.