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Your search keyword '"Rare and undiagnosed diseases"' showing total 3 results
Start Over Descriptor "Rare and undiagnosed diseases" Topic rare diseases
3 results on '"Rare and undiagnosed diseases"'

1. Descriptive epidemiology demonstrating the All of Us database as a versatile resource for the rare and undiagnosed disease community.

Author

Magee DJ, Kicker S, and Thomas A

Subjects
Humans, United States epidemiology, Rare Diseases epidemiology, Rare Diseases diagnosis, Databases, Factual, Electronic Health Records, Undiagnosed Diseases epidemiology
Abstract

Objective: We aim to demonstrate the versatility of the All of Us database as an important source of rare and undiagnosed disease (RUD) data, because of its large size and range of data types., Materials and Methods: We searched the public data browser, electronic health record (EHR), and several surveys to investigate the prevalence, mental health, healthcare access, and other data of select RUDs., Results: Several RUDs have participants in All of Us [eg, 75 of 100 rare infectious diseases (RIDs)]. We generated health-related data for undiagnosed, sickle cell disease (SCD), cystic fibrosis (CF), and infectious (2 diseases) and chronic (4 diseases) disease pools., Conclusion: Our results highlight the potential value of All of Us with both data breadth and depth to help identify possible solutions for shared and disease-specific biomedical and other problems such as healthcare access, thus enhancing diagnosis, treatment, prevention, and support for the RUD community., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Published
2025
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2. Re-analysis of whole-exome sequencing data uncovers novel diagnostic variants and improves molecular diagnostic yields for sudden death and idiopathic diseases.

Author

Salfati EL, Spencer EG, Topol SE, Muse ED, Rueda M, Lucas JR, Wagner GN, Campman S, Topol EJ, and Torkamani A

Subjects
Adenosine Deaminase genetics, Child, Child, Preschool, Databases, Genetic, Female, Genetic Variation, Humans, Male, Myosin Light Chains genetics, Nucleotidases genetics, Phenotype, Rare Diseases genetics, Rare Diseases pathology, Ubiquitin-Protein Ligases genetics, Young Adult, Death, Sudden, Exome genetics, Rare Diseases diagnosis, Exome Sequencing
Abstract

Background: Whole-exome sequencing (WES) has become an efficient diagnostic test for patients with likely monogenic conditions such as rare idiopathic diseases or sudden unexplained death. Yet, many cases remain undiagnosed. Here, we report the added diagnostic yield achieved for 101 WES cases re-analyzed 1 to 7 years after initial analysis., Methods: Of the 101 WES cases, 51 were rare idiopathic disease cases and 50 were postmortem "molecular autopsy" cases of early sudden unexplained death. Variants considered for reporting were prioritized and classified into three groups: (1) diagnostic variants, pathogenic and likely pathogenic variants in genes known to cause the phenotype of interest; (2) possibly diagnostic variants, possibly pathogenic variants in genes known to cause the phenotype of interest or pathogenic variants in genes possibly causing the phenotype of interest; and (3) variants of uncertain diagnostic significance, potentially deleterious variants in genes possibly causing the phenotype of interest., Results: Initial analysis revealed diagnostic variants in 13 rare disease cases (25.4%) and 5 sudden death cases (10%). Re-analysis resulted in the identification of additional diagnostic variants in 3 rare disease cases (5.9%) and 1 sudden unexplained death case (2%), which increased our molecular diagnostic yield to 31.4% and 12%, respectively., Conclusions: The basis of new findings ranged from improvement in variant classification tools, updated genetic databases, and updated clinical phenotypes. Our findings highlight the potential for re-analysis to reveal diagnostic variants in cases that remain undiagnosed after initial WES.

Published
2019
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3. Re-analysis of whole-exome sequencing data uncovers novel diagnostic variants and improves molecular diagnostic yields for sudden death and idiopathic diseases

Author

Emily G. Spencer, Glenn N. Wagner, Ali Torkamani, Jonathan R. Lucas, Eric J. Topol, Manuel Rueda, Steven Campman, Evan D. Muse, Elias L. Salfati, and Sarah E. Topol

Subjects
0301 basic medicine, Male, Myosin Light Chains, lcsh:QH426-470, Adenosine Deaminase, Ubiquitin-Protein Ligases, lcsh:Medicine, 030105 genetics & heredity, Bioinformatics, Sudden death, 03 medical and health sciences, Death, Sudden, Young Adult, Rare Diseases, Molecular autopsy, Nucleotidases, Databases, Genetic, Exome Sequencing, Genetics, Medicine, Humans, Idiopathic disease, Exome, Automated periodic re-analysis, Child, Molecular Biology, Gene, Rare and undiagnosed diseases, Genetics (clinical), Exome sequencing, Likely pathogenic, business.industry, Research, lcsh:R, Medical genetics, Genetic Variation, Sudden unexplained death, Phenotype, 3. Good health, lcsh:Genetics, 030104 developmental biology, Child, Preschool, Whole-exome sequencing, Molecular Medicine, Female, business, Rare disease
Abstract

Background Whole-exome sequencing (WES) has become an efficient diagnostic test for patients with likely monogenic conditions such as rare idiopathic diseases or sudden unexplained death. Yet, many cases remain undiagnosed. Here, we report the added diagnostic yield achieved for 101 WES cases re-analyzed 1 to 7 years after initial analysis. Methods Of the 101 WES cases, 51 were rare idiopathic disease cases and 50 were postmortem “molecular autopsy” cases of early sudden unexplained death. Variants considered for reporting were prioritized and classified into three groups: (1) diagnostic variants, pathogenic and likely pathogenic variants in genes known to cause the phenotype of interest; (2) possibly diagnostic variants, possibly pathogenic variants in genes known to cause the phenotype of interest or pathogenic variants in genes possibly causing the phenotype of interest; and (3) variants of uncertain diagnostic significance, potentially deleterious variants in genes possibly causing the phenotype of interest. Results Initial analysis revealed diagnostic variants in 13 rare disease cases (25.4%) and 5 sudden death cases (10%). Re-analysis resulted in the identification of additional diagnostic variants in 3 rare disease cases (5.9%) and 1 sudden unexplained death case (2%), which increased our molecular diagnostic yield to 31.4% and 12%, respectively. Conclusions The basis of new findings ranged from improvement in variant classification tools, updated genetic databases, and updated clinical phenotypes. Our findings highlight the potential for re-analysis to reveal diagnostic variants in cases that remain undiagnosed after initial WES.

Published
2019

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