RT Journal Article
SR Electronic
T1 Exome and genome sequencing in adults with undiagnosed disease: a prospective cohort study
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 275
OP 283
DO 10.1136/jmedgenet-2020-106936
VO 58
IS 4
A1 Salma Shickh
A1 Mariana Gutierrez Salazar
A1 Kathleen-Rose Zakoor
A1 Conxi Lázaro
A1 Jessica Gu
A1 Jamie Goltz
A1 Dakota Kleinman
A1 Abdul Noor
A1 Sam Khalouei
A1 Chloe Mighton
A1 Emma Reble
A1 Rita Kodida
A1 Yvonne Bombard
A1 Stephanie DiTroia
A1 Samantha Baxter
A1 Nicholas Watkins
A1 Melanie Care
A1 Arnon Adler
A1 Sheri Horsburgh
A1 Oana Morar
A1 Jillian Murphy
A1 Dayna-Lynn Nevay
A1 Marta Szybowska
A1 Melyssa Aronson
A1 Seema Panchal
A1 Ruth Godoy
A1 Spring Holter
A1 Susan Randall Armel
A1 Kara Semotiuk
A1 Christine Elser
A1 Raymond H Kim
A1 David Chitayat
A1 Joyce So
A1 Hanna Faghfoury
A1 Josh Silver
A1 Chantal F Morel
A1 Jordan Lerner-Ellis
YR 2021
UL http://jmg.bmj.com/content/58/4/275.abstract
AB Background Exome and genome sequencing have been demonstrated to increase diagnostic yield in paediatric populations, improving treatment options and providing risk information for relatives. There are limited studies examining the clinical utility of these tests in adults, who currently have limited access to this technology.Methods Patients from adult and cancer genetics clinics across Toronto, Ontario, Canada were recruited into a prospective cohort study evaluating the diagnostic utility of exome and genome sequencing in adults. Eligible patients were ≥18 years of age and suspected of having a hereditary disorder but had received previous uninformative genetic test results. In total, we examined the diagnostic utility of exome and genome sequencing in 47 probands and 34 of their relatives who consented to participate and underwent exome or genome sequencing.Results Overall, 17% (8/47) of probands had a pathogenic or likely pathogenic variant identified in a gene associated with their primary indication for testing. The diagnostic yield for patients with a cancer history was similar to the yield for patients with a non-cancer history (4/18 (22%) vs 4/29 (14%)). An additional 24 probands (51%) had an inconclusive result. Secondary findings were identified in 10 patients (21%); three had medically actionable results.Conclusions This study lends evidence to the diagnostic utility of exome or genome sequencing in an undiagnosed adult population. The significant increase in diagnostic yield warrants the use of this technology. The identification and communication of secondary findings may provide added value when using this testing modality as a first-line test.