Genetic Diagnosis and Clinical Features of Fetuses With Congenital Diaphragmatic Hernia.

Objective: Congenital diaphragmatic hernia (CDH) is a rare abnormality with highly heterogeneous genetic causes. This study investigated chromosomal and monogenic abnormalities in fetal CDH patients and evaluated the efficacy of chromosomal microarray analysis (CMA) and whole-exome sequencing (WES) for genetic diagnosis. The clinical features of the patients were also evaluated.

Contribution of uniparental disomy to fetal growth restriction: a whole-exome sequencing series in a prenatal setting.

Fetal growth restriction (FGR), a leading cause of perinatal morbidity and mortality, is caused by fetal, maternal, and placental factors. Uniparental disomy (UPD) is a rare condition that leads to imprinting effects, low-level mosaic aneuploidies and homozygosity for pathogenic variants. In the present study, UPD events were detected in 5 women with FGR by trio exome sequencing (trio-WES) of a cohort of 150 FGR cases.

Detection of Mosaic Absence of Heterozygosity (AOH) Using Low-Pass Whole Genome Sequencing in Prenatal Diagnosis: A Preliminary Report.

: Mosaicism is a common biological phenomenon in organisms and has been reported in many types of chromosome abnormalities, including the absence of heterozygosity (AOH). Due to the detection limitations of the sequencing approach, mosaic AOH events are rarely assessed in clinical cases. Herein, we report the performance of mosaic AOH identification using a low-pass (5~8-fold) WGS method (termed 'CMA-seq', an abbreviation for 'Chromosome Analysis by Sequencing') in fetal genetic diagnosis.

Prenatal genetic diagnosis of disseminated infantile myofibromatosis: a case report and literature review.

Background: Infantile myofibromatosis (IM) is a rare disorder characterized by the formation of nodules in the skin, muscle, bone, and, more rarely, visceral organs. Very few cases are detected prenatally, and the final diagnosis cannot be made until pathology is completed after birth. Here, we present a case of disseminated form IM (DFIM) with a diagnosis established on prenatal genetic grounds.

[Accidental discovery of copy number variation on chromosome 1 in a fetus with high risk of trisomy 13 suggested by NIPT].

Objective: To validate a fetus with high risk for trisomy 13 suggested by non-invasive prenatal testing (NIPT).

Methods: The fetus was selected as the study subject after the NIPT detection at Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences on February 18, 2019. Clinical data of the pregnant woman was collected.

Evaluation and Analysis of Absence of Homozygosity (AOH) Using Chromosome Analysis by Medium Coverage Whole Genome Sequencing (CMA-seq) in Prenatal Diagnosis.

Objective: Absence of homozygosity (AOH) is a genetic characteristic known to cause human diseases mainly through autosomal recessive or imprinting mechanisms. The importance and necessity of accurate AOH detection has become more clinically significant in recent years. However, it remains a challenging task for sequencing-based methods thus far.

Ex utero intrapartum therapy in infants with congenital diaphragmatic hernia: a propensity score matching analysis.

Objective: Previous studies have shown that ex utero intrapartum therapy (EXIT) is safe and feasible for newborns with congenital diaphragmatic hernia (CDH). This study reports our experience with EXIT in fetuses with CDH in an attempt to explore the efficacy of EXIT on the survival rate of this population.

Methods: A retrospective analysis of the clinical data of 116 children with CDH was conducted.

Impact of the COVID-19 pandemic on congenital diaphragmatic hernia patients: a single-center retrospective study.

Purpose: To investigate the impact of COVID-19 on the treatment of children with congenital diaphragmatic hernia (CDH).

Methods: We retrospectively collected and compared the data of patients with CDH admitted between January 1, 2020 and December 31, 2021(study group) with the CDH patients admitted before the pandemic between January 1, 2018 and December 31, 2019 (control group).

Results: During the pandemic, 41 patients with CDH diagnosed prenatally were transferred to our hospital, and 40 underwent surgical repair.

[Guidelines for the interpretation of fetal chromosomal karyotyping analysis].

Karyotyping analysis is a classical cytogenetic method for the prenatal diagnosis of fetal chromosomal aberrations. In order to standardize fetal chromosomal karyotyping analysis and adapt to the development of medical genetics technology, the Committee for the Prevention and Control of Birth Defect, Chinese Association of Preventive Medicine has organized the formulation of this guideline. The content has covered general requirements and standards for the analysis of fetal chromosomal karyotypes, analysis of chromosomal mosaicisms, and methods for determining the resolution of G-banding, etc.

Factors associated with test failure in pregnant women undergoing cell-free DNA-based testing for fetal trisomy.

Objective: To investigate the factors associated with cell-free DNA test failure, and the optimal subsequent management of these pregnancies.

Methods: This was a retrospective study of 27,363 singleton pregnancies undergoing cell-free DNA testing. Women with cell-free DNA test failure were divided into a high-risk group and a low-risk group according to their indications.

A Rapid PCR-Free Next-Generation Sequencing Method for the Detection of Copy Number Variations in Prenatal Samples.

Next-generation sequencing (NGS) is emerging as a new method for the detection of clinically significant copy number variants (CNVs). In this study, we developed and validated rapid CNV-sequencing (rCNV-seq) for clinical application in prenatal diagnosis. Low-pass whole-genome sequencing was performed on PCR libraries prepared from amniocyte genomic DNA.

Simultaneous Detection of CNVs and SNVs Improves the Diagnostic Yield of Fetuses with Ultrasound Anomalies and Normal Karyotypes.

The routine assessment to determine the genetic etiology for fetal ultrasound anomalies follows a sequential approach, which usually takes about 6-8 weeks turnaround time (TAT). We evaluated the clinical utility of simultaneous detection of copy number variations (CNVs) and single nucleotide variants (SNVs)/small insertion-deletions (indels) in fetuses with a normal karyotype with ultrasound anomalies. We performed CNV detection by chromosomal microarray analysis (CMA) or low pass CNV-sequencing (CNV-seq), and in parallel SNVs/indels detection by trio-based clinical exome sequencing (CES) or whole exome sequencing (WES).

Trisomy 22 with long spina bifida occulta: A case report.

Introduction: Complete non-mosaic trisomy 22 is a fatal chromosomal disorder that only few fetuses can survive over 12 weeks as reported. Prenatal sonographic findings combined with postnatal or postmortem discoveries showed characteristic multi-systematic anomalies.

Patient Concerns: The unborn baby of a 35-year-old pregnant woman was found to have several anomalies during a prenatal sonographic scan, including intrauterine growth retardation, ventricular septal defect, flat facial profile, and unclear bilateral kidney structures.

Adducted thumb as an isolated morphologic finding: an early sonographic sign of impaired neurodevelopment: A STROBE compliant study.

Fetal adducted thumbs have been described in association with hydrocephalus and other abnormalities, but in cases without other structural malformations the determination of prognosis and recurrence risk is challenging. The aim of our study is to analyze the characteristics, natural history, and postnatal outcome of such cases.A retrospective study was conducted over a period of 4 years in a tertiary referral center.

Contribution of maternal copy number variations to false-positive fetal trisomies detected by noninvasive prenatal testing.

Objective: The aim of the study was to determine the contribution and significance of maternal copy number variations (CNVs) to false-positive noninvasive prenatal testing (NIPT) trisomy results.

Methods: A total of 112 021 patients were referred for NIPT. Fetal aneuploidy testing was performed using low coverage massively parallel sequencing, and results reported as chromosome Z-scores.

Copy number variation sequencing-based prenatal diagnosis using cell-free fetal DNA in amniotic fluid.

Objective: The study aimed to determine whether cell-free fetal DNA (cffDNA) present in amniotic fluid supernatant can be used as a surrogate for amniocyte-based diagnosis of fetal chromosomal abnormalities.

Method: Amniocentesis was performed on 28 high-risk pregnancies. Amniocytes and the cffDNA fraction were prepared from the amniotic fluid samples.

Quantitation of fetal DNA fraction in maternal plasma using circulating single molecule amplification and re-sequencing technology (cSMART).

Background: Calculation of the fetal DNA fraction (FF) is important for reliable and accurate noninvasive prenatal testing (NIPT) for fetal genetic abnormalities. The aim of the study was to develop and validate a novel method for FF determination.

Methods: FF was calculated using the chromosome Y (ChrY) sequence read assay and by circulating single molecule amplification and re-sequencing technology of 76 autosomal SNPs.

Genetic counseling, prenatal screening and diagnosis of Down syndrome in the second trimester in women of advanced maternal age: a prospective study.

Background: The incidence of autosomal trisomy in livebirths is strongly dependent on maternal age. Special consideration is given to the provision of prenatal screening and cytogenetic testing to women of advanced maternal age (AMA). The aim of this study was to evaluate the effectiveness of second trimester prenatal screening and amniocentesis for Down syndrome (DS) and compare the trends of choice of screening and amniocentesis among AMA women.