The High Diagnostic Yield of Prenatal Exome Sequencing Followed by 3400 Gene Panel Analysis in 629 Ongoing Pregnancies With Ultrasound Anomalies DOI Creative Commons
Karin E. M. Diderich, Hennie T. Brüggenwirth,

Marieke Joosten

et al.

Prenatal Diagnosis, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 30, 2024

ABSTRACT Background The aim of this study was to evaluate the diagnostic yield routine exome sequencing (ES) in fetuses with ultrasound anomalies. Methods We performed a retrospective analysis ES results 629 isolated or multiple anomalies referred 2019–2022. Variants gene panel consisting approximately 3400 genes associated congenital and/or intellectual disability were analyzed. used trio and filtering for de novo variants, compound heterozygous homozygous X‐linked variants imprinted genes, known pathogenic variants. Results Pathogenic likely (class five four, respectively) identified 14.0% (88/629, 95% CI 11.5%–16.9%) cases. In current cohort, probability detecting monogenetic disorder ∼1:7 1:8.7–1:5.9), ranging from 1:9 (49/424) cases one major anomaly 1:5 (32/147) system Conclusions Our indicate that notable number (1:7) normal chromosomal microarray have (likely) variant can be detected through prenatal ES. These warrant implementation selected cases, including those an on ultrasound.

Language: Английский

Whole Genome Sequencing in Prenatal Diagnostics: The Danish Approach to Guideline Formation and Implementation Within Public Healthcare DOI Creative Commons
Ida Vogel, Lotte Andreasen, Marie Balslev‐Harder

et al.

Prenatal Diagnosis, Journal Year: 2025, Volume and Issue: unknown

Published: March 23, 2025

ABSTRACT Objective To describe the implementation of whole genome sequencing (WGS) in prenatal diagnostics and outline national guideline system facilitating this. Methods Clinical guidelines for WGS were developed implemented by Danish Fetal Medicine Society. Results Guidelines expert consensus following a review 75 studies. Diagnostic yield served as key factor prioritizing various phenotypes, improving diagnostic accuracy informing clinical decisions. Phenotypes include nuchal translucency ≥ 6.0 mm, multiple anomalies, skeletal dysplasia, neuromuscular diseases, non‐immune hydrops fetalis, central nervous malformations, congenital diaphragmatic hernia severe fetal growth restriction (< 3 SDs not explained placental insufficiency). Small regional variations exist indications, bioinformatics, funding, but is now routinely used nationwide these indications. Conclusion The Society's development, emphasizing gradual implementation, has supported relatively uniform integration into diagnostics.

Language: Английский

Citations

0
The Role of Genetic Testing in Congenital Heart Disease DOI
Courtney P. Verscaj, Sarah U. Morton

Current Treatment Options in Cardiovascular Medicine, Journal Year: 2025, Volume and Issue: 27(1)

Published: April 10, 2025

Language: Английский

Citations

0
Current Controversies in Prenatal Diagnosis—Conference Debate 2024: All Fetuses Undergoing Fetal Therapy Should Have Exome Sequencing DOI Creative Commons
Teresa N. Sparks,

Rogelio Cruz Martínez,

Tim Van Mieghem

et al.

Prenatal Diagnosis, Journal Year: 2025, Volume and Issue: unknown

Published: April 13, 2025

This manuscript summarises the debate held at 2024 annual meeting of The International Society for Prenatal Diagnosis (ISPD). Experts discussed whether all fetuses undergoing fetal therapy should undergo exome sequencing. Arguments in favor included that, with increasing experience and better clinical availability, sequencing can yield valuable diagnostic prognostic information beyond what is available from karyotyping microarray. additional often helpful counseling parents provides a understanding conditions, allowing personalised medicine supporting advancements disease-focused therapies. On contrary, however, significant concerns regarding availability health equity were raised. Moreover, potential delays care incurred by may negatively affect outcomes intervention. Finally, as gathered genetic testing or not pregnancy management decisions termination pregnancy, many families choose to undertake testing. arguments both debaters document current controversies general. was also reflected divided audience vote end debate.

Language: Английский

Citations

0
Phenotypic Features of Fourteen Fetal Cases With a PTEN Variant DOI
Qiuxia Yu, Yongling Zhang, Shuyu Li

et al.

Prenatal Diagnosis, Journal Year: 2025, Volume and Issue: unknown

Published: April 22, 2025

ABSTRACT Objective To present the prenatal sonographic features, genomic findings, and pregnancy outcomes of fetuses diagnosed in utero with a PTEN variant. Method This retrospective study analyzed 14 cases variants identified through ultrasound subsequently confirmed by genetic testing. Clinical laboratory data were collected for these cases, encompassing maternal demographics, molecular testing results, outcomes. Results A total (likely) pathogenic included study. Five exhibited abnormalities on second‐trimester scans; specifically, three presented macrocephaly, one showed mild ventriculomegaly, another had cardiac defects (coarctation aorta ventricular septal defect). Nine additional during third trimester. Among nine six displayed macrocephaly or without polyhydramnios ventriculomegaly; case only polyhydramnios; was characterized macrosomia. Eleven involved de novo variants, whereas inherited from parents. Conclusions Macrocephaly emerged as most prevalent sign observed that prompted detection defects. encourages obstetricians to enhance their awareness regarding ‐related disorders presenting macrocephaly.

Language: Английский

Citations

0
Pitfalls of systematic reviews and meta‐analyses to assess the clinical utility of genomic investigations in prenatal diagnosis DOI Open Access
Fionnuala Mone, Daniel L. Rolnik, Alexandros Sotiriadis

et al.

Ultrasound in Obstetrics and Gynecology, Journal Year: 2024, Volume and Issue: 64(6), P. 713 - 715

Published: July 30, 2024

Language: Английский

Citations

2
The bright future of fetal cardiology DOI
Lindsay R. Freud,

Lynn L. Simpson,

Louise Wilkins‐Haug

et al.

Prenatal Diagnosis, Journal Year: 2024, Volume and Issue: 44(6-7), P. 676 - 678

Published: May 27, 2024

Language: Английский

Citations

0
The High Diagnostic Yield of Prenatal Exome Sequencing Followed by 3400 Gene Panel Analysis in 629 Ongoing Pregnancies With Ultrasound Anomalies DOI Creative Commons
Karin E. M. Diderich, Hennie T. Brüggenwirth,

Marieke Joosten

et al.

Prenatal Diagnosis, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 30, 2024

ABSTRACT Background The aim of this study was to evaluate the diagnostic yield routine exome sequencing (ES) in fetuses with ultrasound anomalies. Methods We performed a retrospective analysis ES results 629 isolated or multiple anomalies referred 2019–2022. Variants gene panel consisting approximately 3400 genes associated congenital and/or intellectual disability were analyzed. used trio and filtering for de novo variants, compound heterozygous homozygous X‐linked variants imprinted genes, known pathogenic variants. Results Pathogenic likely (class five four, respectively) identified 14.0% (88/629, 95% CI 11.5%–16.9%) cases. In current cohort, probability detecting monogenetic disorder ∼1:7 1:8.7–1:5.9), ranging from 1:9 (49/424) cases one major anomaly 1:5 (32/147) system Conclusions Our indicate that notable number (1:7) normal chromosomal microarray have (likely) variant can be detected through prenatal ES. These warrant implementation selected cases, including those an on ultrasound.

Language: Английский

Citations

0