DNA sequencing of maternal plasma to detect Down syndrome: an international clinical validation study.
Genet Med
; 13(11): 913-20, 2011 Nov.
Article
em En
| MEDLINE
| ID: mdl-22005709
ABSTRACT
PURPOSE:
Prenatal screening for Down syndrome has improved, but the number of resulting invasive diagnostic procedures remains problematic. Measurement of circulating cell-free DNA in maternal plasma might offer improvement.METHODS:
A blinded, nested case-control study was designed within a cohort of 4664 pregnancies at high risk for Down syndrome. Fetal karyotyping was compared with an internally validated, laboratory-developed test based on next-generation sequencing in 212 Down syndrome and 1484 matched euploid pregnancies. None had been previously tested. Primary testing occurred at a CLIA-certified commercial laboratory, with cross validation by a CLIA-certified university laboratory.RESULTS:
Down syndrome detection rate was 98.6% (209/212), the false-positive rate was 0.20% (3/1471), and the testing failed in 13 pregnancies (0.8%); all were euploid. Before unblinding, the primary testing laboratory also reported multiple alternative interpretations. Adjusting chromosome 21 counts for guanine cytosine base content had the largest impact on improving performance.CONCLUSION:
When applied to high-risk pregnancies, measuring maternal plasma DNA detects nearly all cases of Down syndrome at a very low false-positive rate. This method can substantially reduce the need for invasive diagnostic procedures and attendant procedure-related fetal losses. Although implementation issues need to be addressed, the evidence supports introducing this testing on a clinical basis.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Diagnóstico Pré-Natal
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Análise de Sequência de DNA
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Síndrome de Down
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Doenças Fetais
Tipo de estudo:
Clinical_trials
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Diagnostic_studies
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Observational_studies
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Risk_factors_studies
Limite:
Adult
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Female
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Humans
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Pregnancy
Idioma:
En
Revista:
Genet Med
Assunto da revista:
GENETICA MEDICA
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos