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Plain-language medical vocabulary for precision diagnosis

Nature Genetics volume 50, pages 474–476 (2018)Cite this article

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To the Editor — For undiagnosed patients and those with rare diseases, the affected individuals themselves are an especially critical source of phenotyping information. These patients live with their condition and develop explicit and implicit knowledge about it, whether from multiple clinician evaluations or from other families and patients experiencing diagnosis for similar conditions. From these interactions, they develop a lexicon of relevant terms; these terms are frequently in plain language, but can also include clinical terms. In exceptional cases, patients’ self-phenotyping and investigations have led to clinical diagnosis; for example, Jill Viles, despite skepticism from doctors, managed to not only diagnose herself and her family members but also to discover fundamental biology and improved management of autosomal dominant Emery–Dreifuss muscular dystrophy1. Further, some phenotypes are not readily observed clinically but can be documented by the patient or family; for instance, the Might family (NGLY1) observed that their baby did not produce tears when crying, and they used this feature to help identify other families with the same disease.

Human genetics and precision medicine aim to understand the relationship between genetic variants and diseases. Whole-exome and whole-genome sequencing have transformed the ability to comprehensively characterize genetic variants. Although whole-exome and whole-genome sequencing have led to the discovery of many novel disease-associated genes, the diagnostic yield in patients without a clear clinical diagnosis has been 11–25%2. With approximately 30,000–100,000 called variants in a typical exome or ~4.5 million variants in a typical genome, multiple candidate genes remain after a bioinformatic analysis; additional methods and data are needed to refine the list of candidates.

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Fig. 1: HPO pipeline.

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Acknowledgements

Funding was provided by the US National Institutes of Health (NIH) Monarch Initiative (OD 5R24OD011883; N.A.V., L.C., T.G., C.M., J.A.M., P.N.R., K.S., S.K., M.A.H.) and Patient-Centered Outcomes Research Institute (PCORI) contract number ME-1511-33184 (N.A.V., I.H., C.B., K.S., J.A.M., M.A.H.).

Author information

Authors and Affiliations

  1. Oregon Clinical & Translational Research Institute, Oregon Health & Science University, Portland, OR, USA

    Nicole A. Vasilevsky, Kent Shefchek, Julie A. McMurry & Melissa A. Haendel

  2. Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland, OR, USA

    Nicole A. Vasilevsky & Melissa A. Haendel

  3. School of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA

    Mark E. Engelstad

  4. School of Dentistry, Oregon Health & Science University, Portland, OR, USA

    Erin D. Foster

  5. Jackson Laboratory for Genomic Medicine, Farmington, CT, USA

    Leigh Carmody & Peter N. Robinson

  6. Undiagnosed Disease Network, Boston, MA, USA

    Matt Might

  7. School of Medicine, Vanderbilt University, Nashville, TN, USA

    Chip Chambers

  8. Department of Health, Government of Western Australia, Perth, Western Australia, Australia

    Hugh J. S. Dawkins

  9. National Center for Advancing Translational Sciences, Genetic and Rare Diseases Information Center, Bethesda, MD, USA

    Janine Lewis, Maria G. Della Rocca & Michelle Snyder

  10. Sanford Health Imagenetics, Sioux Falls, SD, USA

    Cornelius F. Boerkoel & Kayli Rageth

  11. Orphanet, Paris, France

    Ana Rath

  12. Genetic Alliance, Washington, DC, USA

    Sharon F. Terry

  13. Genetic Alliance UK, London, UK

    Alastair Kent

  14. Unique, Oxted, UK

    Beverly Searle

  15. Medical School, University of Western Australia, Perth, Western Australia, Australia

    Gareth Baynam

  16. Inspire, Arlington, VA, USA

    Erik Jones

  17. National Organization for Rare Disorders, Quincy, MA, USA

    Pam Gavin

  18. Department of Pediatrics, University of Washington, Seattle, WA, USA

    Michael Bamshad & Jessica Chong

  19. Kinghorn Centre for Clinical Genomics, Garvan Institute, Sydney, New South Wales, Australia

    Tudor Groza

  20. Undiagnosed Disease Program, Bethesda, MD, USA

    David Adams

  21. Center for Data-Driven Discovery in Biomedicine, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Adam C. Resnick & Allison P. Heath

  22. Lawrence Berkeley National Laboratory, Berkeley, CA, USA

    Chris Mungall

  23. Division of Genetics and Genomics, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA

    Ingrid A. Holm & Catherine A. Brownstein

  24. NeuroCure Cluster of Excellence, Charité–Universitätsmedizin Berlin, Berlin, Germany

    Sebastian Köhler

  25. Linus Pauling Institute, Oregon State University, Corvallis, OR, USA

    Melissa A. Haendel

Authors
  1. Nicole A. Vasilevsky
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  2. Erin D. Foster
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  4. Leigh Carmody
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  5. Matt Might
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  8. Janine Lewis
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  9. Maria G. Della Rocca
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  10. Michelle Snyder
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  11. Cornelius F. Boerkoel
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  13. Sharon F. Terry
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  15. Beverly Searle
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  18. Pam Gavin
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  19. Michael Bamshad
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  20. Jessica Chong
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  21. Tudor Groza
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  22. David Adams
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  24. Allison P. Heath
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  26. Ingrid A. Holm
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  28. Catherine A. Brownstein
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  31. Peter N. Robinson
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  32. Sebastian Köhler
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  33. Melissa A. Haendel
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Contributions

M.A.H. conceived the work. N.A.V., E.D.F., M.E.E., L.C., K.R., S.K. and P.N.R. added layperson synonyms to the Human Phenotype Ontology. K.S. and S.K. performed the analysis. J.A.M. designed the figure. N.A.V., E.D.F., M.E.E., L.C., M.M., C.C., H.J.S.D., J.L., M.G.D.R., M.S., C.F.B., A.R., S.F.T., A.K., B.S., G.B., E.J., P.G., M.B., J.C., T.G., D.A., A.C.R., A.P.H., C.M., I.H., K.R., C.B., K.S., J.A.M., P.N.R., S.K. and M.A.H. wrote the manuscript.

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Correspondence to Melissa A. Haendel.

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Vasilevsky, N.A., Foster, E.D., Engelstad, M.E. et al. Plain-language medical vocabulary for precision diagnosis. Nat Genet 50, 474–476 (2018). https://doi.org/10.1038/s41588-018-0096-x

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