Noninvasive prenatal diagnosis in a family at risk for Fraser syndrome

Provenzano, Aldesia; Palazzo, Viviana; Reho, Paolo; Pagliazzi, Angelica; Marozza, Annabella; Farina, Antonio; Zuffardi, Orsetta; Giglio, Sabrina

doi:10.1002/pd.5700

Cited by 5 publications

(8 citation statements)

References 10 publications

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“…Whole exome sequencing (WES) of maternal, paternal and fetal DNA obtained using invasive sampling methods (i.e., trios) has been shown to provide significant diagnostic uplift for rare monogenic conditions [65] . WES utilising cfDNA is an attractive target to screen for single gene disorders in both fetuses with anomalies detected by imaging and also in place of newborn screening programs [66] . In addition, it may provide a solution where invasive sample acquisition is not possible, for example, owing to a particular position of the placenta [67] .…”

Section: Whole Exome Sequencingmentioning

confidence: 99%

“…There have been a few studies on this, with Provenzano et al successfully identifying autosomal recessive pathogenic variants in FRAS1 [67] , and a de novo pathogenic variant in Xlinked STAG2 [68] . Another small study conducted on three pregnancies with structural anomalies detected by imaging, however, identified several technical challenges associated with trio WES on cfDNA [66] . As such, the authors recommend a more targeted approach [66] .…”

Section: Whole Exome Sequencingmentioning

confidence: 99%

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Non-invasive prenatal diagnosis (NIPD): current and emerging technologies

Hanson¹,

Paternoster²,

Povarnitsyn³

et al. 2023

Extracell Vesicles Circ Nucleic Acids

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Prenatal testing is important for the early detection and diagnosis of rare genetic conditions with life-changing implications for the patient and their family. Gaining access to the fetal genotype can be achieved using gold-standard invasive sampling methods, such as amniocentesis and chorionic villus sampling, but these carry a small risk of miscarriage. Non-invasive prenatal diagnosis (NIPD) for select rare monogenic conditions has been in clinical service in England since 2012 and has revolutionised the field of prenatal diagnostics by reducing the number of women undergoing invasive sampling procedures. Fetal-derived genomic material is present in a highly fragmented form amongst the maternal cell-free DNA (cfDNA) in circulation, with sequence coverage across the entire fetal genome. Cell-free fetal DNA (cffDNA) is the foundation for NIPD, and several technologies have been clinically implemented for the detection of paternally inherited and de novo pathogenic variants. Conversely, a low abundance of cffDNA within a high background of maternal cfDNA makes assigning maternally inherited variants to the fetal fraction a significantly more challenging task. Research is ongoing to expand available tests for maternal inheritance to include a broader range of monogenic conditions, as well as to uncover novel diagnostic avenues. This review covers the scope of technologies currently clinically available for NIPD of monogenic conditions and those still in the research pipeline towards implementation in the future.

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Section: Whole Exome Sequencingmentioning

confidence: 99%

Section: Whole Exome Sequencingmentioning

confidence: 99%

Non-invasive prenatal diagnosis (NIPD): current and emerging technologies

Hanson¹,

Paternoster²,

Povarnitsyn³

et al. 2023

Extracell Vesicles Circ Nucleic Acids

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“…Currently research is actively investigating the efficacy of testing for copy number variants 34‐38 and single gene disorders from cfDNA 39‐44 . Although confined placental mosaicism has been reported in a case of a microdeletion, 45 to our knowledge this has not been reported in single gene disorders.…”

Section: Future Directionsmentioning

confidence: 99%

Diagnostic testing after positive results on cell free DNA screening: CVS or Amnio?

Mardy

Norton

2021

Prenatal Diagnosis

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Objective The positive predictive values of cell free DNA (cfDNA) and rates of confined placental mosaicism (CPM), imprinting and other factors vary by chromosome. Methods We sought to review the literature for each of these features for each chromosome and provide recommendations on chorionic villus sampling (CVS) versus amniocentesis after an abnormal cfDNA result. Results For chromosomes with high rates of CPM (trisomy 13, monosomy X and rare autosomal trisomies [RATs]), an amniocentesis should be considered if the first trimester ultrasound is normal. For monosomy X on cfDNA with an unaffected fetus, maternal karyotyping should be considered after normal fetal diagnostic testing. In cfDNA cases with a trisomy involving a chromosome with imprinted genes (6, 7, 11, 14, 15 and 20), CVS should be considered, followed by amniocentesis if abnormal. If the fetus is unaffected, methylation studies should be considered given the risk of uniparental disomy. A third trimester growth ultrasound should be considered for patients with a positive cfDNA screen for a RAT and an unaffected fetus, especially in the case of trisomy 16. For patients with multiple aneuploidy results on cfDNA, a work‐up for maternal malignancy should be considered. Conclusions Clinicians should consider rates of CPM, imprinting, ultrasound findings and maternal factors when considering whether to recommend amniocentesis or CVS after an abnormal cfDNA result.

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“…Cell-free fetal DNA (cffDNA) and genomic DNA (gDNA) extraction and sequencing were performed as previously described [14]…”

Section: Dna Extraction Library Construction and Sequencingmentioning

confidence: 99%

Prenatal Noninvasive Trio-WES in a Case of Pregnancy-Related Liver Disorder

Provenzano

Farina²,

Seidenari³

et al. 2021

Diagnostics

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Liver disease in pregnancy may present as an acute condition related to the gestational period, characterized by pruritus, jaundice, and abnormal liver function. The disease may be misdiagnosed with other liver diseases, some of which may have consequences for fetal health. It is therefore advisable to implement rapid diagnostic strategies to provide information for the management of pregnancy in these conditions. We report the case of a healthy woman with a twin pregnancy from homologous in vitro fertilization (IVF), who in the third trimester presented jaundice and malaise. Biochemical investigations and liver hyperechogenicity raised the suspicion of acute fatty liver disease of pregnancy (AFLP). Non-invasive prenatal whole-exome sequencing (WES) in the trio identified the Phe305Ile heterozygous variant in the ATP8B1 gene. Considering the twin pregnancy, the percentage of the variant versus the wild allele was of 31%, suggesting heterozygosity present in the mother alone. This analysis showed that the mother was affected by benign recurrent intrahepatic cholestasis of pregnancy (ICP1: # 147480) and indicated the opportunity to anticipate childbirth to avoid worsening of the mother’s health. WES after the birth of the twins confirmed the molecular data.

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Noninvasive prenatal diagnosis in a family at risk for Fraser syndrome

Cited by 5 publications

References 10 publications

Non-invasive prenatal diagnosis (NIPD): current and emerging technologies

Non-invasive prenatal diagnosis (NIPD): current and emerging technologies

Diagnostic testing after positive results on cell free DNA screening: CVS or Amnio?

Prenatal Noninvasive Trio-WES in a Case of Pregnancy-Related Liver Disorder

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