Ju Zheng

Prenatal evaluation of the conus medullaris position in normal fetuses and fetuses with spina bifida occulta using three‐dimensional ultrasonography

This study aimed to assess the fetal conus medullaris (CM) position with three‐dimensional (3D) ultrasonography and its use in detecting and diagnosing spina bifida occulta (SBO).

Fetal Right Aortic Arch: Associated Anomalies, Genetic Anomalies with Chromosomal Microarray Analysis and Postnatal Outcome

The aim of the study was to assess the associated prenatal findings, genetic anomalies with chromosomal microarray analysis (CMA) and postnatal outcome of fetal right aortic arch (RAA).

Fetal persistent left superior vena cava in cases with and without chromosomal anomalies

The objectives of this study are to determine and compare the prevalence of persistent left superior vena cava (PLSVC) in chromosomally normal and abnormal fetuses and to evaluate the potential of PLSVC as a screening marker for chromosomal abnormalities.

Date-Independent Parameters: an Innovative Method to Assess Fetal Cerebellar Vermis

The objectives of this paper were to identify gestational age-independent parameters for cerebellar vermis (CV) evaluation and examine their use in CV integrity assessments. Using three-dimensional ultrasonography, we obtained the following measurements from 217 pregnant women carrying 18–37-week-old fetuses: the largest area of the CV, vermal craniocaudal distance (VCC), vermal anterior to posterior diameter, and vermal perimeter (VP). In addition, fetal growth parameters (biparietal diameter, head circumference femoral length [FL], humeral length, transverse cerebellar diameter, and abdominal circumference) were evaluated. The ratios of the CV dimensions to each other and to the fetal growth parameters were calculated. Ratios showing no significant correlation with gestational age and acceptable internal validity in subsequent bootstrap analyses were chosen. The normal ranges of the specific parameters were compared with cases identified with posterior fossa anomalies (PFA). The ratios VP/FL (mean 1.20, SD 0.09), VCC/FL (mean 0.36, SD 0.03), and VCC/VP (mean 0.3, SD 0.03) were chosen using our protocol. These parameters were not significantly different between normal fetuses and those with PFA and an intact vermis. However, VP/FL and VCC/FL values were abnormal in cases of hypoplastic vermis or vermian agenesis, while the VP/VCC value was abnormal only in cases of vermian agenesis. The VP/FL, VCC/FL, and VCC/VP ratios are gestational age-independent parameters in evaluation of CV integrity.

Four-Dimensional Sonography With Spatiotemporal Image Correlation and Tomographic Ultrasound Imaging in the Prenatal Diagnosis of Anomalous Pulmonary Venous Connections

To determine whether the use of 4‐dimensional (4D) sonography with spatiotemporal image correlation (STIC) and tomographic ultrasound imaging (TUI) can provide additional information with respect to 2‐dimensional (2D) echocardiography in the prenatal diagnosis of anomalous pulmonary venous connections.

Prenatal diagnosis of prevalence of the right heart: associated anomalies and outcome predictors.

To analyze the characteristics, associations, and outcomes of prevalence of the right heart and to evaluate the use of sonography to predict the risk of a poor prognosis in fetuses with this condition.

Prenatal diagnosis of chromosomal aberrations in fetuses with conotruncal heart defects by genome-wide high-resolution SNP array

Abstract Objectives: To explore chromosomal variations, including copy number variations (CNVs), in fetuses with conotruncal heart defect (CTD). Methods: During a 5-year period, a total of 129 fetuses with ascertained CTDs were investigated for chromosomal abnormalities using quantitative fluorescence PCR (QF-PCR) and chromosomal microarray analysis (CMA). Fetuses were divided into two subgroups: benign group (with normal QF-PCR results and benign CNVs) and nonbenign group [with aneuploidies, nonbenign CNVs [pathogenic CNVs and CNVs of unknown significance (VOUS)]. Data on fetal structural malformations, chromosomal variations, and pregnancy outcomes were collected and compared. Results: Of the 129 cases, 17 were found to have common aneuploidies. In the remaining 112 cases with normal a QF-PCR result, pathogenic CNVs, CNVs of VOUS, and benign CNVs were identified in 5.3, 5.3, and 4.5%, respectively. Compared with benign group, fetuses in nonbenign group had a significantly higher rate of neurologic defects (13.8 versus 3.0%, p < .05), overall extracardiac anomalies (86.2 versus 45.0%, p < .05), and perinatal death (57.1 versus 18.4%, p < .05), whereas, no significant difference in that of associated cardiovascular anomalies was noted (48.2 versus 46.0%, p = .29). Among the extracardiac anomalies, thymus abnormalities were strongly associated with nonbenign CNVs (33.3 versus 1% of fetuses in benign group, p < .05). Conclusions: Pathogenic CNVs, in addition to chromosomal aneuploidies, contributed to the pathogenesis of CTD. The presence of associated extracardiac anomalies including thymus abnormalities correlated with a higher probability of nonbenign chromosomal variations, which was associated with an unfavorable outcome.

Identification of compound heterozygous variants in the noncoding RNU4ATAC gene in a Chinese family with two successive foetuses with severe microcephaly

BackgroundWhole-exome sequencing (WES) over the last few years has been increasingly employed for clinical diagnosis. However, one caveat with its use is that it inevitably fails to detect disease-causative variants that occur within noncoding RNA genes. Our experience in identifying pathogenic variants in the noncoding RNU4ATAC gene, in a Chinese family where two successive foetuses had been affected by severe microcephaly, is a case in point. These foetuses exhibited remarkably similar phenotypes in terms of their microcephaly and brain abnormalities; however, the paucity of other characteristic phenotypic features had made a precise diagnosis impossible. Given that no external causative factors had been reported/identified during the pregnancies, we sought a genetic cause for the phenotype in the proband, the second affected foetus.ResultsA search for chromosomal abnormalities and pathogenic copy number variants proved negative. WES was also negative. These initial failures prompted us to consider the potential role of RNU4ATAC, a noncoding gene implicated in microcephalic osteodysplastic primordial dwarfism type-1 (MOPD1), a severe autosomal recessive disease characterised by dwarfism, severe microcephaly and neurological abnormalities. Subsequent targeted sequencing of RNU4ATAC resulted in the identification of compound heterozygous variants, one being the most frequently reported MOPD1-causative mutation (51G>A), whereas the other was a novel 29T>A variant. Four distinct lines of evidence (allele frequency in normal populations, evolutionary conservation of the affected nucleotide, occurrence within a known mutational hotspot for MOPD1-causative variants and predicted effect on RNA secondary structure) allowed us to conclude that 29T>A is a new causative variant for MOPD1.ConclusionsOur findings highlight the limitations of WES in failing to detect variants within noncoding RNA genes and provide support for a role for whole-genome sequencing as a first-tier genetic test in paediatric medicine. Additionally, the identification of a novel RNU4ATAC variant within the mutational hotspot for MOPD1-causative variants further strengthens the critical role of the 5′ stem-loop structure of U4atac in health and disease. Finally, this analysis enabled us to provide prenatal diagnosis and genetic counselling for the mother’s third pregnancy, the first report of its kind in the context of inherited RNU4ATAC variants.

Chromosomal aneuploidies and copy number variations in posterior fossa abnormalities diagnosed by prenatal ultrasonography

To explore the genetic aetiology of fetal posterior fossa abnormalities (PFAs).

Chromosomal and subchromosomal anomalies associated to small for gestational age fetuses with no additional structural anomalies

Objectives: To assess the chromosomal and subchromosomal anomalies in small for gestational age (SGA) fetuses with no additional structural anomalies and their clinical outcomes.