Clinical and technical assessment of MedExome vs. NGS panels in patients with suspected genetic disorders in Southwestern Ontario.
J Hum Genet
; 66(5): 451-464, 2021 May.
Article
em En
| MEDLINE
| ID: mdl-33093641
ABSTRACT
The adaptation of a broad genomic sequencing approach in the clinical setting has been accompanied by considerations regarding the clinical utility, technical performance, and diagnostic yield compared to targeted genetic approaches. We have developed MedExome, an integrated framework for sequencing, variant calling (SNVs, Indels, and CNVs), and clinical assessment of ~4600 medically relevant genes. We compared the technical performance of MedExome with the whole-exome and targeted gene-panel sequencing, assessed the reasons for discordance, and evaluated the added clinical yield of MedExome in a cohort of unresolved subjects suspected of genetic disease. Our analysis showed that despite a higher average read depth in panels (3058 vs. 855), MedExome yielded full coverage of the enriched regions (>20X) and 99% variant concordance rate with panels. The discordance rate was associated with low-complexity regions, high-GC content, and low allele fractions, observed in both platforms. MedExome yielded full sensitivity in detecting clinically actionable variants, and the assessment of 138 patients with suspected genetic conditions resulted in 76 clinical reports (31 full [22.1%], 3 partial, and 42 uncertain/possible molecular diagnoses). MedExome sequencing has comparable performance in variant detection to gene panels. Added diagnostic yield justifies expanded implementation of broad genomic approaches in unresolved patients; however, cost-benefit and health systems impact warrants assessment.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Técnicas de Diagnóstico Molecular
/
Sequenciamento de Nucleotídeos em Larga Escala
/
Sequenciamento do Exoma
/
Doenças Genéticas Inatas
Tipo de estudo:
Diagnostic_studies
/
Evaluation_studies
Limite:
Humans
País/Região como assunto:
America do norte
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article