Whole-Exome Sequencing in the Clinic: Lessons from Six Consecutive Cases from the Clinician's Perspective

Amber Volk; Erin Conboy; Beverly Wical; Marc Patterson; Salman Kirmani

doi:10.1159/000371598

Whole-Exome Sequencing in the Clinic: Lessons from Six Consecutive Cases from the Clinician's Perspective

Mol Syndromol. 2015 Feb;6(1):23-31. doi: 10.1159/000371598. Epub 2015 Feb 3.

Authors

Amber Volk¹, Erin Conboy², Beverly Wical³, Marc Patterson⁴, Salman Kirmani⁵

Affiliations

¹ Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, Minn., USA.
² Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minn., USA.
³ Department of Pediatric Neurology, Gillette Children's Hospital and Clinic, St. Paul, Minn., USA.
⁴ Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minn., USA ; Department of Medical Genetics, Mayo Clinic, Rochester, Minn., USA ; Division of Child and Adolescent Neurology, Mayo Clinic, Rochester, Minn., USA.
⁵ Department of Medical Genetics, Mayo Clinic, Rochester, Minn., USA.

Abstract

Whole-exome sequencing (WES) is being used clinically to diagnose rare Mendelian disorders, especially when standard tests have failed. The diagnostic yield from WES is reported to be ∼15-30%; however, data regarding the clinical utility and interpretative challenges from the clinician's perspective are lacking. Here, we present a series of the first 6 unselected consecutive cases seen over a period of 6 months where WES was employed in clinical labs via trio-based testing (proband and parents). While we do not discount the value of WES in the clinical setting, our cases and experience illustrate the significant clinical challenges of WES, even when a diagnosis may be achieved.

Keywords: Diagnostic odyssey; Schinzel-Giedion syndrome; Whole-exome sequencing.

Publication types

Review