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In the version of this article originally published, some cases that were presented in Fig. 3 should have been underlined but were not. The appropriate cases have now been underlined. The error has been corrected in the print, PDF and HTML versions of the article.
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Current non-invasive prenatal screening is targeted toward the detection of chromosomal abnormalities in the fetus1,2. However, screening for many dominant monogenic disorders associated with de novo mutations is not available, despite their relatively high incidence3. Here we report on the development and validation of, and early clinical experience with, a new approach for non-invasive prenatal sequencing for a panel of causative genes for frequent dominant monogenic diseases. Cell-free DNA (cfDNA) extracted from maternal plasma was barcoded, enriched, and then analyzed by next-generation sequencing (NGS) for targeted regions. Low-level fetal variants were identified by a statistical analysis adjusted for NGS read count and fetal fraction. Pathogenic or likely pathogenic variants were confirmed by a secondary amplicon-based test on cfDNA. Clinical tests were performed on 422 pregnancies with or without abnormal ultrasound findings or family history. Follow-up studies on cases with available outcome results confirmed 20 true-positive, 127 true-negative, zero false-positive, and zero-false negative results. The initial clinical study demonstrated that this non-invasive test can provide valuable molecular information for the detection of a wide spectrum of dominant monogenic diseases, complementing current screening for aneuploidies or carrier screening for recessive disorders.
Asunto(s)
Enfermedades Genéticas Congénitas/diagnóstico , Anomalías Múltiples/diagnóstico por imagen , Anomalías Múltiples/genética , Acondroplasia/diagnóstico , Acondroplasia/genética , Acrocefalosindactilia/diagnóstico , Acrocefalosindactilia/genética , Adulto , Huesos/anomalías , Ácidos Nucleicos Libres de Células , Colágeno Tipo I/genética , Cadena alfa 1 del Colágeno Tipo I , Síndrome de Cornelia de Lange/diagnóstico , Síndrome de Cornelia de Lange/genética , Femenino , Enfermedades Genéticas Congénitas/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Hidropesía Fetal/diagnóstico por imagen , Hidropesía Fetal/genética , Linfangioma Quístico/diagnóstico por imagen , Linfangioma Quístico/genética , Medida de Translucencia Nucal , Osteogénesis Imperfecta/diagnóstico , Osteogénesis Imperfecta/genética , Valor Predictivo de las Pruebas , Embarazo , Diagnóstico Prenatal , Análisis de Secuencia de ADN , Displasia Tanatofórica/diagnóstico , Displasia Tanatofórica/genética , Ultrasonografía PrenatalRESUMEN
The objective of this study was to determine the role of health beliefs in genetic amniocentesis acceptance in a diverse racial-ethnic population. Participants completed a previously-validated questionnaire consisting of three sections: (1) demographics, (2) amniocentesis knowledge, and (3) health beliefs, which assessed perceived susceptibility, seriousness of potential impact, benefits of testing, and barriers to testing. The results showed that Hispanic women were less likely to accept amniocentesis (51.5% vs. Caucasian 82.8%, African American 82.9%, Asian 82.8%). Education level was the only demographic factor higher among acceptors. Women who accepted amniocentesis had higher perceived seriousness, susceptibility, and benefits HBM scores and higher knowledge scores than women who declined. HBM scores and knowledge predicted the amniocentesis decision correctly 91.5% of the time. Individual health beliefs and knowledge play a greater role in genetic amniocentesis acceptance than do demographic factors such as race-ethnicity.