HYPO- AND HYPERADRENAL STATES - SALT DEPRIVATION STUDY

肾上腺低下和肾上腺亢进状态 - 盐剥夺研究

• 批准号: 7380558
• 负责人: MARIA I. NEW
• 金额: $ 0.97万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-17 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7380558
• 关键词: emotions; enzymes; family; gene mutation; genes; genetics; genotype; molecular genetics; phenotype; salts; steroid biosynthesis

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.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。大量的遗传性和获得性疾病可以影响肾上腺皮质的功能，导致肾上腺皮质功能降低（hypo）或增加（hyper）。我们的研究小组致力于阐明类固醇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。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，并建立了专门针对酶缺陷的治疗方法。在引起疾病的基因突变已被表征（例如21-羟化酶缺乏症，占所有CAH病例的90-95%）并且疾病机制已知的情况下，这可以是直接的;然而，在决定因素基因尚未被鉴定并且疾病机制仍然未知的情况下，这可能特别困难。因此，以下方案概述了我们能够表征罕见类固醇生成酶缺陷患者及其家庭成员的不同临床谱的方法。 与CAH相关的假设：1。基因型可预测盐耗、单纯男性化和21-羟化酶缺乏引起的非经典型先天性肾上腺皮质增生（CAH）患者的表型。2.有一些基因型与表型不一致的例子，特别是关于耗盐的显著特征，值得研究。