Solving Medical Mysteries: Miller School Renewed as Site for Undiagnosed Diseases Network
Article Summary
- An NIH grant will allow geneticists and scientists with the John T. Macdonald Department of Human Genetics to continue partnering with colleagues to accelerate the diagnosis of rare conditions.
- The Miller School is one of 12 sites to serve as Diagnostic Centers of Excellence for phase III of the Undiagnosed Diseases Network.
- As part of the UDN, Miller School researchers have investigated nearly 100 cases and solved about 30 percent of them.
The University of Miami Miller School of Medicine has once again been funded as a site for the National Institute of Health’s Undiagnosed Diseases Network (UDN), bringing hope for answers and treatment to Florida’s most baffling health conditions.
The four-year grant will allow geneticists and scientists with the Miller School’s prestigious John T. Macdonald Department of Human Genetics to continue partnering with colleagues around the country to improve and accelerate the diagnosis of rare and mysterious conditions by using the latest technology and team science to collectively solve the toughest cases.
A Collaborative Research Project
As one of a dozen sites to serve as Diagnostic Centers of Excellence for phase III of the UDN, the Miller School maintains access to both technical and practical support. The network provides genome sequencing. If there is enough suspicion for a mutation, the doctors and scientists consult with experts in fruit flies, zebra fish and worms who model mutations in detected variants to look for causation. Then they all meet, usually weekly over Zoom and occasionally in person, to exchange ideas on diagnosing and treating this complicated group of patients.
“We’ve identified quite a few new genes and some new disorders,” said Mustafa Tekin, M.D., professor and Chair of the John T. Macdonald Department of Human Genetics and a member of the John P. Hussman Institute for Human Genomics at the Miller School as well as contact principal investigator of the UDN Miami site. “Some of these patients were actually able to follow up with some potential treatments. This is a good example of precision medicine specifically focused on a gene an individual has.”
“This is a very important program, and for the University of Miami to be a part of it is a very big deal,” said Stephan Züchner, M.D., Ph.D., chief genomics officer and professor in the John T. Macdonald Department of Human Genetics and UDN co-principal investigator at the Miller School. “It underlines the national reputation of UM in this field and it is a valuable resource for the people in our community who can participate in this very specialized program.”
A History of Research and Discovery
The Miller School will continue to build on its record of excellence, uncovering new diagnoses in patients that have led to effective treatments for some. Since its selection to join the UDN in 2018, Miller School doctors and researchers from a variety medical specialties have investigated upwards of 100 cases.
They’ve solved about 30 percent of them, matching other elite institutions, and publish their discoveries in peer-edited journals, sharing the newfound knowledge beyond the UDN.
“All these diagnoses are rare and missed by the general medicine clinical investigations, and we get together and try to solve medical mysteries by using clinical expertise and deep laboratory investigations, including whole genome sequencing,” Dr. Tekin said.
In total, the UDN – first launched by the NIH in 2013 and today led by the National Institute of Neurological Disorders and Stroke (NINDS) – has diagnosed 780 people who spent years searching for answers for their symptoms. Unsolved cases are periodically reevaluated. The need is enormous, with an estimated 25 million Americans suffering from rare disorders.
“These patients and their families have often been through an extended diagnostic odyssey,” Dr. Züchner said. “When these patients finally receive a genetic diagnosis, the focus can shift to identifying a therapy, including upcoming gene-targeting therapies.”
Families seeking a diagnosis can apply to the UDN through a central website portal. Until now, the Miller School team has reviewed all of the Florida applications, collecting additional records before deciding whether to take the case.
Moving forward under new guidance in phase III, the team will accept all applicants and provide guidance, even if they do not continue with an in-depth analysis. Historically, half the patients have come from within the University and the other half have been referred from health systems throughout the state. The Miller School is proud that the diversity of its patient pool is representative of the state’s demographics.
Tags: Dr. Mustafa Tekin, Dr. Stephan Zuchner, Gene sequencing, genetics, genome research, Undiagnosed Diseases Network