Clinical validation of a noninvasive prenatal test for genomewide detection of fetal copy number variants.
Am J Obstet Gynecol
; 215(2): 227.e1-227.e16, 2016 Aug.
Article
em En
| MEDLINE
| ID: mdl-26899906
ABSTRACT
BACKGROUND:
Current cell-free DNA assessment of fetal chromosomes does not analyze and report on all chromosomes. Hence, a significant proportion of fetal chromosomal abnormalities are not detectable by current noninvasive methods. Here we report the clinical validation of a novel noninvasive prenatal test (NIPT) designed to detect genomewide gains and losses of chromosomal material ≥7 Mb and losses associated with specific deletions <7 Mb.OBJECTIVE:
The objective of this study is to provide a clinical validation of the sensitivity and specificity of a novel NIPT for detection of genomewide abnormalities. STUDYDESIGN:
This retrospective, blinded study included maternal plasma collected from 1222 study subjects with pregnancies at increased risk for fetal chromosomal abnormalities that were assessed for trisomy 21 (T21), trisomy 18 (T18), trisomy 13 (T13), sex chromosome aneuploidies (SCAs), fetal sex, genomewide copy number variants (CNVs) ≥7 Mb, and select deletions <7 Mb. Performance was assessed by comparing test results with findings from G-band karyotyping, microarray data, or high coverage sequencing.RESULTS:
Clinical sensitivity within this study was determined to be 100% for T21 (95% confidence interval [CI], 94.6-100%), T18 (95% CI, 84.4-100%), T13 (95% CI, 74.7-100%), and SCAs (95% CI, 84-100%), and 97.7% for genomewide CNVs (95% CI, 86.2-99.9%). Clinical specificity within this study was determined to be 100% for T21 (95% CI, 99.6-100%), T18 (95% CI, 99.6-100%), and T13 (95% CI, 99.6-100%), and 99.9% for SCAs and CNVs (95% CI, 99.4-100% for both). Fetal sex classification had an accuracy of 99.6% (95% CI, 98.9-99.8%).CONCLUSION:
This study has demonstrated that genomewide NIPT for fetal chromosomal abnormalities can provide high resolution, sensitive, and specific detection of a wide range of subchromosomal and whole chromosomal abnormalities that were previously only detectable by invasive karyotype analysis. In some instances, this NIPT also provided additional clarification about the origin of genetic material that had not been identified by invasive karyotype analysis.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Diagnóstico Pré-Natal
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Aberrações Cromossômicas
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Transtornos Cromossômicos
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Variações do Número de Cópias de DNA
Tipo de estudo:
Diagnostic_studies
/
Observational_studies
/
Prognostic_studies
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Risk_factors_studies
Limite:
Adolescent
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Adult
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Female
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Humans
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Middle aged
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Pregnancy
Idioma:
En
Revista:
Am J Obstet Gynecol
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Canadá