Background on the Undiagnosed Disease Network
The Undiagnosed Diseases Network (UDN) is a research study initiated in 2015, funded by the National Institutes of Health Common Fund, with a goal of assembling clinical and research experts throughout the U.S. The network has several key goals:
- Provide a diagnosis for individuals with the most challenging mysterious medical problems.
- Facilitate research using cutting edge technologies to find causes of these diseases.
- Create an integrated research community and share knowledge to improve patient care.
The UDN has a coordinating center at Harvard Medical School. In addition, they have 12 clinical sites located throughout the U.S. One of the sites is located in Houston, Texas at Baylor College of Medicine. Currently, Baylor Genetics serves as the sole sequencing core for the UDN providing both exome and genome sequencing to the network.
While there are many rare diseases going undiagnosed, participants have to meet certain criteria before they can work with the UDN. Ideal applicants include those with medical findings where no diagnosis has been made despite evaluation by two or more different specialists. A letter of recommendation from a care provider is needed in order to be considered for the study, which should include:
- A summary of the medical problems
- Previous diagnoses
- History of testing and evaluations
- List of treatments and medications
- The providers thoughts and recommendations
- Family history
In addition, a willingness to store and share their biomaterials and data with other research sites is a requirement to participate.
Accomplishments and Outcomes
Since September 2015, the UDN has received 4,752 applications and 1,877 of those applications have been approved for the study.
Of the patients evaluated, 454 (29%) have received certain or highly likely diagnoses. Out of those 454 patients, 81% received their diagnoses through exome or genome sequencing. Typically the patient and their family members (usually parents) are sequenced concurrently to aid in the interpretation of variants. Other testing such as gene panels, chromosomal microarray, or newer testing methods, such as RNA sequencing, contributed to the other 19% of diagnoses. Interestingly, there have been at least 30 patients with newly defined conditions and 14 participants have more than one diagnosis. Many of these diagnostic successes have been made possible due to collaborative input and sharing of knowledge from experts at the UDN sites during ongoing in-person and virtual conferences.
From the research side, there have been many discoveries. The Model Organism Screening Center has used fruit fly, nematode worm, and zebrafish to evaluate the functional significance of 321 genetic variants found in UDN participants. In addition, the metabolomics core of the UDN has provided comprehensive analyses for 179 UDN participants to assess the biochemical mechanisms in their diseases. RNA sequencing, provided at several of the UDN sites, has been used to better understand the gene expression and potential diagnoses of 107 UDN participants.
The UDN is committed to sharing their data in the most sustainable and responsible ways possible to reach many communities with a goal to help others with similar diseases. Some of the accomplishments of the UDN include:
- 110+ scientific publications published in peer-reviewed scientific journals
- Genomic data shared in dbGap
- 470 variant interpretations submitted to ClinVar
- 1,419 records shared to the Matchmaker Exchange
- 176 participant pages located on the UDN Website
The UDN & Baylor Genetics
Baylor Genetics has been a partner with the UDN since the beginning of the study. From 2015 – 2018, BG provided interpretation and reporting for UDN exome sequencing cases during phase 1 of the UDN studies. Currently, since September 2018, BG is the UDN’s sole sequencing core for all exome and genome sequencing during phase 2 of its studies. BG is proud to serve this prestigious network with our state-of-the-art sequencing and help provide answers to patients and their families. While there are many individuals working on this project, BG has core members actively participating with this study:
- Christine Eng, MD, is the Chief Medical Officer and Chief Quality Officer at Baylor Genetics, a professor at Baylor College of Medicine, and a principal investigator of the exome and genome sequencing core for the UDN. She is the Medical Director of the Baylor Genetics labs.
- Pengfei Liu, PhD, is the Associate Clinical Director of the NGS at Baylor Genetics and directs the Lab Genetics and Genomics Training Program. In addition, he is an assistant professor at Baylor College of Medicine. As an investigator for the UDN, he specializes in the clinical implementation of exome and genome sequencing and in the reanalysis of genomic sequence data.
- Patricia Ward, MS, CGC, is a Senior Genetic Counselor at Baylor Genetics and an associate professor at Baylor College of Medicine. She is an investigator for the UDN and provides guidance, support, and reporting for the UDN clinical sites.