When moments matter: Finding answers with rapid exome sequencing.

Zöe Powis,John M Graham,Margaret Au,Natalie Gallant,Brian Schoenfeld,Kirsten Blanco,Sha Tang,Kathryn Singh,Erika Palmaer,Linda M Randolph,Meghan Towne,Deepali N Shinde,Jesse Hunter,Kelly D Farwell Hagman

doi:10.1002/mgg3.1027

Abstract

BackgroundWhen time is of the essence in critical care cases, a fast molecular diagnosis is often necessary to help health care providers quickly determine best next steps for treatments, prognosis, and counseling of their patients. In this paper, we present the diagnostic rates and improved quality of life for patients undergoing clinical rapid exome sequencing.MethodsThe clinical histories and results of 41 patients undergoing rapid exome sequencing were retrospectively reviewed.ResultsClinical rapid exome sequencing identified a definitive diagnosis in 13/41 (31.7%) and other relevant findings in 17 of the patients (41.5%). The average time to verbal report was 7 days; to written report was 11 days.ConclusionsOur observations demonstrate the utility and effectiveness of rapid family‐based diagnostic exome sequencing in improving patients care.

Highlights

Exome sequencing is a powerful technology that diagnoses roughly 30% of patients with a broad spectrum of unknown genetic conditions, a rate that is two to three times that of traditional genetic testing methods (Farwell Hagman et al, 2016; Farwell et al, 2014; Iglesias et al, 2014; Lee et al, 2014; Yang et al, 2014), at about half to one‐quarter of the cost (Monroe et al, 2016; Soden et al, 2014)
Health care providers were discouraged from using exome sequencing in certain situations as it did not “support short turnaround times” (ACMG Board of Directors, 2012)
A faster turnaround time (TAT) impacts the clinical utility of exome sequencing as highlighted in one study showing that results were deemed clinically beneficial in 32.6% of diagnosed patients with standard TAT, and 65% in patients with rapid exome sequencing

Summary

| INTRODUCTION

Exome sequencing is a powerful technology that diagnoses roughly 30% of patients with a broad spectrum of unknown genetic conditions, a rate that is two to three times that of traditional genetic testing methods (Farwell Hagman et al, 2016; Farwell et al, 2014; Iglesias et al, 2014; Lee et al, 2014; Yang et al, 2014), at about half to one‐quarter of the cost (Monroe et al, 2016; Soden et al, 2014). A shortened diagnostic journey in neonates has been shown to aid the process for appropriate, targeted | 2 of 7 treatments, accurate prognosis, and counseling (Willig et al, 2015) These first studies investigated only a small number of patients in selected populations (such as prenatal or neonatal) undergoing rapid exome (Chandler et al, 2018; Willig et al, 2015). We present detailed clinical characteristics of an unselected group of individuals undergoing rapid exome testing to determine a diagnostic rate and investigate its utility. Statistical analysis was performed using the Fisher's exact test

| Ethical compliance

| RESULTS

| DISCUSSION

Findings

CONFLICT OF INTEREST