Implementation of genomic medicine for rare disease in a tertiary healthcare system: Mayo Clinic Program for Rare and Undiagnosed Diseases (PRaUD)
Authors: Pinto e Vairo Filippo , Kemppainen Jennifer L. , Vitek Carolyn R. Rohrer , Whalen Denise A. , Kolbert Kayla J. , Sikkink Kaitlin J. , Kroc Sarah A. , Kruisselbrink Teresa , Shupe Gabrielle F. , Knudson Alyssa K. , Burke Elizabeth M. , Loftus Elle C. , Bandel Lorelei A. , Prochnow Carri A. , Mulvihill Lindsay A. , Thomas Brittany , Gable Dale M. , Graddy Courtney B. , Garzon Giovanna G. Moreno , Ekpoh Idara U. , Porquera Eva M. Carmona , Fervenza Fernando C. , Hogan Marie C. , El Ters Mireille , Warrington Kenneth J. , Davis John M. , Koster Matthew J. , Orandi Amir B. , Basiaga Matthew L. , Vella Adrian , Kumar Seema , Creo Ana L. , Lteif Aida N. , Pittock Siobhan T. , Tebben Peter J. , Abate Ejigayehu G. , Joshi Avni Y. , Ristagno Elizabeth H. , Patnaik Mrinal S. , Schimmenti Lisa A. , Dhamija Radhika , Sabrowsky Sonia M. , Wierenga Klaas J. , Keddis Mira T. , Samadder Niloy Jewel J. , Presutti Richard J. , Robinson Steven I. , Stephens Michael C. , Roberts Lewis R. , Faubion William A. , Driscoll Sherilyn W. , Wong-Kisiel Lily C. , Selcen Duygu , Flanagan Eoin P. , Ramanan Vijay K. , Jackson Lauren M. , Mauermann Michelle L. , Ortega Victor E. , Anderson Sarah A. , Aoudia Stacy L. , Klee Eric W. , McAllister Tammy M. , Lazaridis Konstantinos N. 
Published: June 2023

Background

In the United States, rare disease (RD) is defined as a condition that affects fewer than 200,000 individuals. Collectively, RD affects an estimated 30 million Americans. A significant portion of RD has an underlying genetic cause; however, this may go undiagnosed. To better serve these patients, the Mayo Clinic Program for Rare and Undiagnosed Diseases (PRaUD) was created under the auspices of the Center for Individualized Medicine (CIM) aiming to integrate genomics into subspecialty practice including targeted genetic testing, research, and education.

Methods

Patients were identified by subspecialty healthcare providers from 11 clinical divisions/departments. Targeted multi-gene panels or custom exome/genome-based panels were utilized. To support the goals of PRaUD, a new clinical service model, the Genetic Testing and Counseling (GTAC) unit, was established to improve access and increase efficiency for genetic test facilitation. The GTAC unit includes genetic counselors, genetic counseling assistants, genetic nurses, and a medical geneticist. Patients receive abbreviated point-of-care genetic counseling and testing through a partnership with subspecialty providers.

Results

Implementation of PRaUD began in 2018 and GTAC unit launched in 2020 to support program expansion. Currently, 29 RD clinical indications are included in 11 specialty divisions/departments with over 142 referring providers. To date, 1152 patients have been evaluated with an overall solved or likely solved rate of 17.5% and as high as 66.7% depending on the phenotype. Noteworthy, 42.7% of the solved or likely solved patients underwent changes in medical management and outcome based on genetic test results.

Conclusion

Implementation of PRaUD and GTAC have enabled subspecialty practices advance expertise in RD where genetic counselors have not historically been embedded in practice. Democratizing access to genetic testing and counseling can broaden the reach of patients with RD and increase the diagnostic yield of such indications leading to better medical management as well as expanding research opportunities.