ANALYSIS OF CUSHING DISEASE WHOLE EXOME SEQUENCING DATA 2020

库欣病 (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通常是由分泌ACTH的垂体肿瘤引起的。值得注意的是，CD患者还存在面部高度和鼻长异常等异常特征。 由于我们在 CD 方面的工作，我们对其他垂体和内分泌疾病产生了兴趣，这需要与下面针对 CD 进行的相同工作。 这个 合作非常成功地产生了现已发表在医学文献中的重要发现。 校内人口健康研究部 (DIPHR) 和校内研究部 (DIR) 一直在通过全外显子组测序 (WES) 合作寻找与 CD 相关的遗传变异。 WES 是一种高效、经济的方法，用于询问负责编码蛋白质的遗传密码。 随着WES技术在库欣病研究中的应用，产生了大量的数据用于分析。 这项工作卓有成效，迄今为止已在该领域发表了 6 篇论文。由于本研究中发现的大量变异远远超出了最初的预期以及与对照的比较，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 临床中心的 CD 和其他病例的 WES 数据，继续扩展我们对 CD 的了解。 病例将从具有最佳相关临床和实验室数据的病例中选择。

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.