The Exome Clinic and the role of medical genetics expertise in the interpretation of exome sequencing results

Dustin Baldridge, Jennifer Heeley, Marisa Vineyard, Linda Manwaring, Tomi L. Toler, Emily Fassi, Elise Fiala, Sarah Brown, Charles W. Goss, Marcia Willing, Dorothy K. Grange, Beth A. Kozel, Marwan Shinawi

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

Purpose:Evaluation of the clinician's role in the optimal interpretation of clinical exome sequencing (ES) results.Methods:Retrospective chart review of the first 155 patients who underwent clinical ES in our Exome Clinic and direct interaction with the ordering geneticist to evaluate the process of interpretation of results.Results:The most common primary indication was neurodevelopmental problems (∼66%), followed by multiple congenital anomalies (∼10%). Based on sequencing data, the overall diagnostic yield was 36%. After assessment by the medical geneticist, incorporation of detailed phenotypic and molecular data, and utilization of additional diagnostic modalities, the final diagnostic yield increased to 43%. Seven patients in our cohort were included in initial case series that described novel genetic syndromes, and 23% of patients were involved in subsequent research studies directly related to their results or involved in efforts to move beyond clinical ES for diagnosis. Clinical management was directly altered due to the ES findings in 12% of definitively diagnosed cases.Conclusions:Our results emphasize the usefulness of ES, demonstrate the significant role of the medical geneticist in the diagnostic process of patients undergoing ES, and illustrate the benefits of postanalytical diagnostic work-up in solving the "diagnostic odyssey.

Original languageEnglish
Pages (from-to)1040-1048
Number of pages9
JournalGenetics in Medicine
Volume19
Issue number9
DOIs
StatePublished - Sep 1 2017

Keywords

  • Exome Clinic
  • diagnostic yield
  • exome sequencing
  • genetic counseling
  • medical geneticist

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