Dataset Information

Clinical sites of the Undiagnosed Diseases Network: unique contributions to genomic medicine and science.

ABSTRACT:

Purpose

The NIH Undiagnosed Diseases Network (UDN) evaluates participants with disorders that have defied diagnosis, applying personalized clinical and genomic evaluations and innovative research. The clinical sites of the UDN are essential to advancing the UDN mission; this study assesses their contributions relative to standard clinical practices.

Methods

We analyzed retrospective data from four UDN clinical sites, from July 2015 to September 2019, for diagnoses, new disease gene discoveries and the underlying investigative methods.

Results

Of 791 evaluated individuals, 231 received 240 diagnoses and 17 new disease-gene associations were recognized. Straightforward diagnoses on UDN exome and genome sequencing occurred in 35% (84/240). We considered these tractable in standard clinical practice, although genome sequencing is not yet widely available clinically. The majority (156/240, 65%) required additional UDN-driven investigations, including 90 diagnoses that occurred after prior nondiagnostic exome sequencing and 45 diagnoses (19%) that were nongenetic. The UDN-driven investigations included complementary/supplementary phenotyping, innovative analyses of genomic variants, and collaborative science for functional assays and animal modeling.

Conclusion

Investigations driven by the clinical sites identified diagnostic and research paradigms that surpass standard diagnostic processes. The new diagnoses, disease gene discoveries, and delineation of novel disorders represent a model for genomic medicine and science.

SUBMITTER: Schoch K

PROVIDER: S-EPMC7867619 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Publications

Clinical sites of the Undiagnosed Diseases Network: unique contributions to genomic medicine and science.

Schoch Kelly K Esteves Cecilia C Bican Anna A Spillmann Rebecca R Cope Heidi H McConkie-Rosell Allyn A Walley Nicole N Fernandez Liliana L Kohler Jennefer N JN Bonner Devon D Reuter Chloe C Stong Nicholas N Mulvihill John J JJ Novacic Donna D Wolfe Lynne L Abdelbaki Ayat A Toro Camilo C Tifft Cyndi C Malicdan May M Gahl William W Liu Pengfei P Newman John J Goldstein David B DB Hom Jason J Sampson Jacinda J Wheeler Matthew T MT Cogan Joy J Bernstein Jonathan A JA Adams David R DR McCray Alexa T AT Shashi Vandana V

Genetics in medicine : official journal of the American College of Medical Genetics 20201023 2

<h4>Purpose</h4>The NIH Undiagnosed Diseases Network (UDN) evaluates participants with disorders that have defied diagnosis, applying personalized clinical and genomic evaluations and innovative research. The clinical sites of the UDN are essential to advancing the UDN mission; this study assesses their contributions relative to standard clinical practices.<h4>Methods</h4>We analyzed retrospective data from four UDN clinical sites, from July 2015 to September 2019, for diagnoses, new disease gen ...[more]

PMID: 33093671

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Project description:Genetic counselors (GCs) are increasingly filling important positions on research study teams, but there is limited literature describing the roles of GCs in these settings. GCs on the Undiagnosed Diseases Network (UDN) study team serve in a variety of roles across the research network and provide an opportunity to better understand genetic counselor roles in research. To quantitatively characterize the tasks regularly performed and professional fulfillment derived from these tasks, two surveys were administered to UDN GCs in a stepwise fashion. Responses from the first, free-response survey elicited the scope of tasks which informed development of a second structured, multiple-select survey. In survey 2, respondents were asked to select which roles they performed. Across 19 respondents, roles in survey 2 received a total of 947 selections averaging approximately 10 selections per role. When asked to indicate what roles they performed, respondent selected a mean of 50 roles (range 22-70). Survey 2 data were analyzed via thematic coding of responses and hierarchical cluster analysis to identify patterns in responses. From the thematic analysis, 20 non-overlapping codes emerged in seven categories: clinical interaction and care, communication, curation, leadership, participant management, research, and team management. Three themes emerged from the categories that represented the roles of GCs in the UDN: clinical care, collaboration, and curation. Cluster analyses showed that responses were more similar among individuals at the same institution than between institutions. This study highlights the ways GCs apply their unique skill set in the context of a clinical translational research network. Additionally, findings from this study reinforce the wide applicability of core skills that are part of genetic counseling training. Clinical literacy, genomics expertise and analysis, interpersonal, psychosocial and counseling skills, education, professional practice skills, and an understanding of research processes make genetic counselors well suited for such roles and poised to positively impact research experiences and outcomes for participants.

Project description:BACKGROUND:The majority of undiagnosed diseases manifest with objective findings that warrant further investigation. The Undiagnosed Diseases Network (UDN) receives applications from patients whose symptoms and signs have been intractable to diagnosis; however, many UDN applicants are affected primarily by subjective symptoms such as pain and fatigue. We sought to characterize presenting symptoms, referral sources, and demographic factors of applicants to the UDN to identify factors that may determine application outcome and potentially differentiate between those with undiagnosed diseases (with more objective findings) and those who are less likely to have an undiagnosed disease (more subjective symptoms). METHODS:We used a systematic retrospective review of 151 consecutive Not Accepted and 50 randomly selected Accepted UDN applications. The primary outcome was whether an applicant was Accepted, or Not Accepted, and, if accepted, whether or not a diagnosis was made. Objective and subjective symptoms and information on prior specialty consultations were collected from provider referral letters. Demographic data and decision data on network acceptance were gathered from the UDN online portal. RESULTS:Fewer objective findings and more subjective symptoms were found in the Not Accepted applications. Not Accepted referrals also were from older individuals, reported a shorter period of illness, and were referred to the UDN by their primary care physicians. All of these differences reached statistical significance in comparison with Accepted applications. The frequency of subspecialty consults for diagnostic purposes prior to UDN application was similar in both groups. CONCLUSIONS:The preponderance of subjective and lack of objective findings in the Not Accepted applications distinguish these from applicants that are accepted for evaluation and diagnostic efforts through the UDN. Not Accepted applicants are referred primarily by their primary care providers after multiple specialist consultations fail to yield answers. Distinguishing between patients with undiagnosed diseases with objective findings and those with primarily subjective findings can delineate patients who would benefit from further diagnostic processes from those who may have functional disorders and need alternative pathways for management of their symptoms. TRIAL REGISTRATION:clinicaltrials.gov NCT02450851 , posted May 21st 2015.

Dataset Information

Clinical sites of the Undiagnosed Diseases Network: unique contributions to genomic medicine and science.

Purpose

Methods

Results

Conclusion

Publications

Clinical sites of the Undiagnosed Diseases Network: unique contributions to genomic medicine and science.

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