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Genetic test utilization and diagnostic yield in adult patients with neurological disorders

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Abstract

To determine the diagnostic yield of different genetic test modalities in adult patients with neurological disorders, we evaluated all adult patients seen for genetic diagnostic evaluation in the outpatient neurology practice at the University of Pennsylvania between January 2016 and April 2017 as part of the newly created Penn Neurogenetics Program. Subjects were identified through our electronic medical system as those evaluated by the Program’s single clinical genetic counselor in that period. A total of 377 patients were evaluated by the Penn Neurogenetics Program in different settings and genetic testing recommended. Of those, 182 (48%) were seen in subspecialty clinic setting and 195 (52%) in a General Neurogenetics Clinic. Genetic testing was completed in over 80% of patients in whom it was recommended. The diagnostic yield was 32% across disease groups. Stratified by testing modality, the yield was highest with directed testing (50%) and array comparative genomic hybridization (45%), followed by gene panels and exome testing (25% each). In conclusion, genetic testing can be successfully requested in clinic in a large majority of adult patients. Age is not a limiting factor for a genetic diagnostic evaluation and the yield of clinical testing across phenotypes (almost 30%) is consistent with previous phenotype-focused or research-based studies. These results should inform the development of specific guidelines for clinical testing and serve as evidence to improve reimbursement by insurance payers.

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Funding

This study was supported by the Neurogenetics Translational Center of Excellence, Department of Neurology, University of Pennsylvania.

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Authors and Affiliations

  1. Department of Neurology, University of Pennsylvania, 330 South 9th Street, Second Floor, Philadelphia, PA, 19107, USA

    Tanya M. Bardakjian, Ingo Helbig, Colin Quinn, Lauren B. Elman, Leo F. McCluskey, Steven S. Scherer & Pedro Gonzalez-Alegre

  2. The Children’s Hospital of Philadelphia, Philadelphia, USA

    Ingo Helbig & Pedro Gonzalez-Alegre

Authors
  1. Tanya M. Bardakjian
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  2. Ingo Helbig
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  3. Colin Quinn
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  4. Lauren B. Elman
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  5. Leo F. McCluskey
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  6. Steven S. Scherer
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  7. Pedro Gonzalez-Alegre
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Corresponding author

Correspondence to Pedro Gonzalez-Alegre.

Ethics declarations

This study was approved by the Institutional Review Committee at the University of Pennsylvania. As an IRB-approved retrospective analysis, approval to conduct this study by an ethical standards committee was received.

Electronic supplementary material

Supplementary Table 1

Variants of unknown significance. The tab named “VUS” indicates those variants still unresolved at the end of the study. The Tab named “Resolution Pathogenic” indicates VUS reclassified as pathogenic. MAF: minor allele frequency in ExAC. Note that the number of VUS remaining is higher than the final number of patients with VUS, as subjects can have multiple VUS. (XLSX 21 kb)

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Bardakjian, T.M., Helbig, I., Quinn, C. et al. Genetic test utilization and diagnostic yield in adult patients with neurological disorders. Neurogenetics 19, 105–110 (2018). https://doi.org/10.1007/s10048-018-0544-x

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  • DOI: https://doi.org/10.1007/s10048-018-0544-x

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