Non-invasive prenatal testing for fetal inheritance of maternal ß-thalassaemia mutations using targeted sequencing and relative mutation dosage: a feasibility study.
BJOG
; 125(4): 461-468, 2018 Mar.
Article
em En
| MEDLINE
| ID: mdl-29211324
ABSTRACT
OBJECTIVE:
To evaluate whether targeted sequencing and relative mutation dosage can be used to diagnose correctly inheritance of maternal ß-thalassaemia mutations in cell-free DNA.DESIGN:
Feasibility study using samples collected in a prenatal clinic.SETTING:
South East Asia. POPULATION Couples where both partners were known to be carriers of one of four common ß-thalassaemia mutations or an HbE mutation, and therefore at risk of carrying a fetus affected with ß-thalassaemia.METHODS:
49 samples previously identified as having inherited a paternal ß-thalassaemia mutation were amplified using nested polymerase chain reaction (PCR), and then sequencing. Relative mutation dosage was used to classify the fetus as having inherited the wild-type or mutant maternal allele. MAIN OUTCOMEMEASURES:
Classification of the fetus as 'unaffected' (if the maternal wild-type allele was inherited) or 'affected' with ß-thalassaemia (if the maternal mutant allele was inherited).RESULTS:
A classification for inheritance of maternal allele was obtained in 48/49 samples (98.0%). A concordant call was made in 44/48 cases (91.7%) one false-positive and three false-negatives were obtained. Thus, we had an overall sensitivity of 87.5% [95% confidence interval (CI) 67.6-97.3%] and a specificity of 95.8% (95% CI 78.9-99.9%) for inheritance of maternal genotype.CONCLUSIONS:
RMD for detection of inheritance of maternal ß-thalassaemia mutations has potential for clinical use. Our sequential approach could be applied to other single-gene disorders. TWEETABLE ABSTRACT NIPT for ß-thalassaemia achieved using nested-PCR followed by relative mutation dosage.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Diagnóstico Pré-Natal
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Análise de Sequência de DNA
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Talassemia beta
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Doenças Fetais
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Mutação
Tipo de estudo:
Diagnostic_studies
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Prognostic_studies
Limite:
Adult
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Female
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Humans
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Male
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Pregnancy
País como assunto:
Asia
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article