The usefulness of whole-exome sequencing in routine clinical practice

Genet Med. 2014 Dec;16(12):922-31. doi: 10.1038/gim.2014.58. Epub 2014 Jun 5.


Purpose: Reports of the use of whole-exome sequencing in clinical practice are limited. We report our experience with whole-exome sequencing in 115 patients in a single center and evaluate its feasibility and clinical usefulness in clinical care.

Methods: Whole-exome sequencing was utilized based on the judgment of three clinical geneticists. We describe age, gender, ethnicity, consanguinity, indication for testing, family history, insurance, laboratory results, clinician interpretation of results, and impact on patient care.

Results: Most patients were children (78.9%). The most common indications for testing were birth defects (24.3%) and developmental delay (25.2%). We identified four new candidate human disease genes and possibly expanded the disease phenotypes associated with five different genes. Establishing a diagnosis led to discontinuation of additional planned testing in all patients, screening for additional manifestations in eight, altered management in fourteen, novel therapy in two, identification of other familial mutation carriers in five, and reproductive planning in six.

Conclusion: Our results show that whole-exome sequencing is feasible, has clinical usefulness, and allows timely medical interventions, informed reproductive choices, and avoidance of additional testing. Our results also suggest phenotype expansion and identification of new candidate disease genes that would have been impossible to diagnose by other targeted testing methods.

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Consanguinity
  • DNA Mutational Analysis / methods*
  • Developmental Disabilities / diagnosis
  • Developmental Disabilities / genetics
  • Exome*
  • Female
  • Genetic Testing
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Infant
  • Infant, Newborn
  • Karyotyping
  • Male
  • Mutation
  • Pedigree
  • Phenotype
  • Pregnancy
  • Reproducibility of Results
  • Retrospective Studies
  • Young Adult