lunes, 19 de agosto de 2013

The utility of the traditional medical genetics diagnostic evaluation in the context of next-generation sequencing for undiagnosed genetic disorders : Genetics in Medicine : Nature Publishing Group

The utility of the traditional medical genetics diagnostic evaluation in the context of next-generation sequencing for undiagnosed genetic disorders : Genetics in Medicine : Nature Publishing Group

The utility of the traditional medical genetics diagnostic evaluation in the context of next-generation sequencing for undiagnosed genetic disorders

Genetics in Medicine


Published online



The purpose of this study was to assess the diagnostic yield of the traditional, comprehensive clinical evaluation and targeted genetic testing, within a general genetics clinic. These data are critically needed to develop clinically and economically grounded diagnostic algorithms that consider presenting phenotype, traditional genetics testing, and the emerging role of next-generation sequencing (whole-exome/genome sequencing).


We retrospectively analyzed a cohort of 500 unselected consecutive patients who received traditional genetic diagnostic evaluations at a tertiary medical center. We calculated the diagnosis rate, number of visits to diagnosis, genetic tests, and the cost of testing.


Thirty-nine patients were determined to not have a genetic disorder; 212 of the remaining 461 (46%) received a genetic diagnosis, and 72% of these were diagnosed on the first visit. The cost per subsequent successful genetic diagnosis was estimated at $25,000.


Almost half of the patients were diagnosed using the traditional approach, most at the initial visit. For those remaining undiagnosed, next-generation sequencing may be clinically and economically beneficial. Estimating a 50% success rate for next-generation sequencing in undiagnosed genetic disorders, its application after the first clinical visit could result in a higher rate of genetic diagnosis at a considerable cost savings per successful diagnosis.

Genet Med advance online publication 8 August 2013


genetic diagnosis; genetic testing; medical genetics evaluation; next-generation sequencing; undiagnosed genetic disorder

At a glance



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Author information


  1. Department of Pediatrics, Division of Medical Genetics, Duke University Medical Center, Durham, North Carolina, USA

    • Vandana Shashi,

    • Allyn McConkie-Rosell,

    • Bruce Rosell,

    • Kelly Schoch,

    • Kasturi Vellore,

    • Marie McDonald &

    • Yong-Hui Jiang

  2. Center for Human Genome Variation, Duke University Medical Center, Durham, North Carolina, USA

    • Pingxing Xie,

    • Anna Need &

    • David G Goldstein

Corresponding author

Correspondence to:

Supplementary information

Word documents

  1. Supplementary Table S1 (32 KB)

  2. Supplementary Table S2 (30 KB)

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