Vanderbilt Center for Undiagnosed Diseases (VCUD): Expansion of the NIH Undiagnosed Disease Program to an Undiagnosed Disease Network (UDN) will bring expertise and compassionate care to UD patients, give them hope and improve their lives. Vanderbilt is an ideal milieu for the growth and development of the VCUD, our UDN Clinical Site, because our culture fosters excellence in patient oriented care and research. We have a large and productive Clinical and Translational Science Award (CTSA) that hosts one of the largest Clinical Research Centers (CRC) in the country. Our CTSA includes a cohort of outstanding clinicians and physician scientists whose diagnostic and research skills are broad and deep. We will combine established Vanderbilt resources including the StarPanel electronic medical record (EMR), the REDCap database system, and the BioVU DNA databank with other Vanderbilt assets to create the VCUD. The VCUD will provide the right team to make the right diagnosis for a UD patient the first time. We will then use Vanderbilt VICTR Studios and the Mass Spectrometry Research Center to discover new diseases and promote translational research that leads to new treatments. We will also test for genetic variations that we find in UD candidate genes in the >13,000, soon to be >40,000 exomes in our BioVU system that links de-identified EMRs to DNA samples from >166,000 Vanderbilt patients. Our BioVU cohort will also allow us to identify patients with phenotypic similarities to each UD, as well as, the Rare Diseases (RD) and New Diseases (ND) that may be included in a specific UD. We will then use the BioVU data and DNAs to determine the contribution of notable allelic variants found in VCUD patients to more general phenotypes that may be more common. We have experience with and a passion to diagnose, treat and care for UD patients at Vanderbilt and we look forward to creating a VCUD that brings hope and resolution to desperate situations and fosters synergistic collaboration with the UDN. The VCUD will contribute to the UDN by becoming a clinical arm of the Human Genome Project that efficiently screens, invites, evaluates, diagnoses, counsels and assists UD patients and their physicians in maximizing the quality of their lives. To develop the VCUD we will use unique resources at Vanderbilt that will efficiently diagnose UD patients of all ages and foster development of the UDN by the following Specific Aims: 1) Improve the diagnosis and care of pediatric and adult UD patients using the right VCUD team to make the right diagnosis the first time using ResearchMatch, StarPanel and REDCap;2) Determine the etiology of UD by collecting and sharing data with the UDN;and determine the pathophysiology, and develop better diagnostic and treatment options, including clinical trials by using VICTR Studios to focus multiple Vanderbilt resources on UD;and 3) Use the Vanderbilt Mass Spectrometry Research Center, BioVU repository and VANGARD to discover, characterize and determine the contributions of both new diseases and atypical presentations of rare diseases to the Undiagnosed Diseases that affect many patients.
The Vanderbilt Center for Undiagnosed Disease will function in the NIH funded Network of Undiagnosed Diseases to evaluate persons afflicted with undiagnosed illnesses and to share information with the Network that will best ensure that an accurate and timely diagnosis can be made, that counseling and advice be given to the patient and care givers, and that newly described diseases be appropriately studied and researched in order to improve health of the patient and to assist in diagnosing and treating similar patients in the whole human population.
|Sivley, R Michael; Sheehan, Jonathan H; Kropski, Jonathan A et al. (2018) Three-dimensional spatial analysis of missense variants in RTEL1 identifies pathogenic variants in patients with Familial Interstitial Pneumonia. BMC Bioinformatics 19:18|
|Splinter, Kimberly; Adams, David R; Bacino, Carlos A et al. (2018) Effect of Genetic Diagnosis on Patients with Previously Undiagnosed Disease. N Engl J Med 379:2131-2139|
|Pomerantz, Daniel J; Ferdinandusse, Sacha; Cogan, Joy et al. (2018) Clinical heterogeneity of mitochondrial NAD kinase deficiency caused by a NADK2 start loss variant. Am J Med Genet A 176:692-698|
|Cassini, Thomas A; Robertson, Amy K; Bican, Anna G et al. (2018) Phenotypic heterogeneity of ZMPSTE24 deficiency. Am J Med Genet A 176:1175-1179|
|Ramoni, Rachel B; Mulvihill, John J; Adams, David R et al. (2017) The Undiagnosed Diseases Network: Accelerating Discovery about Health and Disease. Am J Hum Genet 100:185-192|
|Zastrow, Diane B; Zornio, Patricia A; Dries, Annika et al. (2017) Exome sequencing identifies de novo pathogenic variants in FBN1 and TRPS1 in a patient with a complex connective tissue phenotype. Cold Spring Harb Mol Case Stud 3:a001388|
|Shashi, Vandana; Pena, Loren D M; Kim, Katherine et al. (2016) De Novo Truncating Variants in ASXL2 Are Associated with a Unique and Recognizable Clinical Phenotype. Am J Hum Genet 99:991-999|
|Bashamboo, Anu; Donohoue, Patricia A; Vilain, Eric et al. (2016) A recurrent p.Arg92Trp variant in steroidogenic factor-1 (NR5A1) can act as a molecular switch in human sex development. Hum Mol Genet 25:3446-3453|
|Chen, Xinping; Talati, Megha; Fessel, Joshua P et al. (2016) Estrogen Metabolite 16?-Hydroxyestrone Exacerbates Bone Morphogenetic Protein Receptor Type II-Associated Pulmonary Arterial Hypertension Through MicroRNA-29-Mediated Modulation of Cellular Metabolism. Circulation 133:82-97|
|Cogan, Joy D; Kropski, Jonathan A; Zhao, Min et al. (2015) Rare variants in RTEL1 are associated with familial interstitial pneumonia. Am J Respir Crit Care Med 191:646-55|
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