ANALYSIS OF CUSHING DISEASE WHOLE EXOME SEQUENCING DATA 2020

库欣氏病（CD）是一种垂体产生不适当水平的促肾上腺皮质激素（ACTH）的疾病。 ACTH刺激肾上腺产生过量的皮质醇，导致临床疾病。CD通常由分泌ACTH的垂体瘤引起。值得注意的是，CD患者也有异常的特征，包括异常的面部高度和鼻长。 从我们在CD方面的工作出发，我们对其他垂体和内分泌疾病产生了兴趣，这些疾病需要与下文所述CD相同的工作。 这 合作非常成功，产生了现已在医学文献中发表的重要发现。 校内人口健康研究部（DIPHR）和校内研究部（DIPHR）一直在合作，通过全外显子组测序（WES）寻找与CD相关的遗传变异。 WES是一种高效、经济的方法来询问负责编码蛋白质的遗传密码。 将WES技术应用于库欣病的研究，产生了大量的数据进行分析。 这项工作卓有成效，迄今已在这一领域发表了6篇论文。由于本研究中发现的大量变异远远超过了最初的预期和与对照的比较，我们继续加强对拷贝数变异的搜索。 该任务订单将通过分析NIH临床中心关于CD和其他病例的WES数据，继续扩展我们对CD的了解。 将从具有最佳相关临床和实验室数据的病例中选择病例。

Cushing's disease (CD) is a condition in which the pituitary gland produces inappropriate levels of adrenocorticotropic hormone (ACTH). ACTH stimulates the adrenal gland to produce excess cortisol, leading to clinical disease. CD is commonly caused by ACTH secreting pituitary tumors. It is noteworthy that patients who have CD also have abnormal features including abnormal facial height and nasal length. Stemming from our work in CD, we have developed an interest in other pituitary and endocrine conditions which requires the same work as indicated for CD below. This collaboration has been very successful in producing important discoveries now published in the medical literature. The Division of Intramural Population Health Research (DIPHR) and the Division of Intramural Research (DIR) have been collaborating in the search for genetic variants associated with CD via whole exome sequencing (WES). WES is an efficient, cost effective method to interrogate the genetic code responsible for coding proteins. With the use of WES technology in the studying of the Cushing disease a large amount of data was generated for analysis. The work has been highly productive and made possible the publication of 6 papers to date in this area. With the large number of variants discovered in this study far exceeding the original expectation and comparison to controls, we continue to enhance our search for copy number variants. This task order will continue to expand our knowledge of CD by analyzing the WES data on CD and other cases at the NIH clinical center. Cases will be selected from those with the best associated clinical and laboratory data.