ANALYSIS OF CUSHING DISEASE WHOLE EXOME SEQUENCING DATA 2020

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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 in collaboration with Dr. Constantine Stratakis at the NIH clinical center. Cases will be selected from those with the best associated clinical and laboratory data.