The Utility of the Traditional Medical Genetics Diagnostic Evaluation in the Context of Next-Generation Sequencing for Undiagnosed Genetic Disorders

Genet Med. 2014 Feb;16(2):176-82. doi: 10.1038/gim.2013.99. Epub 2013 Aug 29.

Abstract

Purpose: 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).

Methods: 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.

Results: 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.

Conclusion: 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.

MeSH terms

  • Algorithms
  • Exome
  • Female
  • Genetic Diseases, Inborn / diagnosis*
  • Genetic Diseases, Inborn / genetics
  • Genetic Testing / economics
  • Genetic Testing / methods*
  • Genome, Human
  • High-Throughput Nucleotide Sequencing / economics
  • High-Throughput Nucleotide Sequencing / methods*
  • Humans
  • Male
  • Retrospective Studies
  • Sequence Analysis, DNA / economics
  • Sequence Analysis, DNA / methods*