Improved diagnostic yield compared with targeted gene sequencing panels suggests a role for whole-genome sequencing as a first-tier genetic test.
Genet Med
; 20(4): 435-443, 2018 04.
Article
em En
| MEDLINE
| ID: mdl-28771251
ABSTRACT
PurposeGenetic testing is an integral diagnostic component of pediatric medicine. Standard of care is often a time-consuming stepwise approach involving chromosomal microarray analysis and targeted gene sequencing panels, which can be costly and inconclusive. Whole-genome sequencing (WGS) provides a comprehensive testing platform that has the potential to streamline genetic assessments, but there are limited comparative data to guide its clinical use.MethodsWe prospectively recruited 103 patients from pediatric non-genetic subspecialty clinics, each with a clinical phenotype suggestive of an underlying genetic disorder, and compared the diagnostic yield and coverage of WGS with those of conventional genetic testing.ResultsWGS identified diagnostic variants in 41% of individuals, representing a significant increase over conventional testing results (24%; P = 0.01). Genes clinically sequenced in the cohort (n = 1,226) were well covered by WGS, with a median exonic coverage of 40 × ±8 × (mean ±SD). All the molecular diagnoses made by conventional methods were captured by WGS. The 18 new diagnoses made with WGS included structural and non-exonic sequence variants not detectable with whole-exome sequencing, and confirmed recent disease associations with the genes PIGG, RNU4ATAC, TRIO, and UNC13A.ConclusionWGS as a primary clinical test provided a higher diagnostic yield than conventional genetic testing in a clinically heterogeneous cohort.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Testes Genéticos
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Análise de Sequência de DNA
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Predisposição Genética para Doença
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Estudos de Associação Genética
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Sequenciamento Completo do Genoma
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Doenças Genéticas Inatas
Tipo de estudo:
Diagnostic_studies
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Prognostic_studies
Limite:
Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article