Linhuan Huang

Increased expression and altered methylation of HERVWE1 in the human placentas of smaller fetuses from monozygotic, dichorionic, discordant twins.

Background The human endogenous retroviral family W, Env(C7), member 1 gene (HERVWE1) is thought to participate in trophoblast cell fusion, and its expression is diminished in the placentas of singleton intrauterine growth-retarded pregnancies. However, there is limited information about the role of HERVWE1 in discordant fetal growth in twins. This study was to compare HERVWE1 gene expression between the placentas of discordant monozygotic twins and to identify its regulation by methylation. Methodology/Principal Findings Fetuses from twenty-one pairs of monozygotic, dichorionic, discordant twins were marked as “smaller” or “larger” according to birth weight. Placental HERVWE1 mRNA and protein expression profiles were analyzed using quantitative RT-PCR and immunohistochemistry (IHC) staining. Methylation profiles of the HERVWE1 promoter region were analyzed using a pyrosequencing assay. DNA methyltransferase (DNMT) transcript levels were analyzed by RT-PCR. 5-methyl cytosine (5-MC) was stained using an immunohistochemical assay. There was a significant negative correlation between HERVWE1 mRNA levels and birth weight in twins (P<0.01). Whereas the mean methylation level of the HERVWE1 promoter region was diminished in the smaller group in discordant twins(P<0.01), increased mRNA and protein levels of HERVWE1 were found in smaller fetuses compared with larger fetuses in discordant twins(P<0.01). There was no significant difference in 5-MC staining intensity between discordant twins (P>0.05). The DNMT3b3 mRNA levels in the smaller group were significantly downregulated compared with the larger group in discordant twins(P<0.05), whereas the DNMT3b7 mRNA levels in the smaller group were significantly upregulated compared with the larger group in discordant twins(P<0.05). Conclusions/Significance In discordant, monozygotic, dichorionic twins, HERVWE1 expression was higher in smaller fetuses and lower in larger fetuses. Methylation of the HERVWE1 gene promoter region may participate in the regulation of HERVWE1 gene expression in discordant twin pregnancies.

Application of chromosomal microarray analysis in prenatal diagnosis of fetal growth restriction.

To investigate the clinical value of chromosomal microarray analysis (CMA) in the prenatal diagnosis of chromosomal abnormalities in fetal growth restriction (FGR) cases.

Prenatal diagnosis of submicroscopic chromosomal aberrations in fetuses with ventricular septal defects by chromosomal microarray-based analysis

To evaluate the usefulness of chromosomal microarray analysis in fetuses with ventricular septal defects (VSDs) with or without associated anomalies and normal karyotype.

Preeclampsia in twin pregnancies: association with selective intrauterine growth restriction

Abstract Objective: To identify the association between preeclampsia (PE) and selective intrauterine growth restriction (sIUGR) in twin pregnancies. Methods: This was a retrospective cohort study of 1004 twin pregnancies from 2008 to 2014. We specifically compared the incidence, clinical characteristics and outcomes of PE between sIUGR and normal-growth twin pregnancies. Results: PE occurred more frequently in sIUGR pregnancies [29.0% (51/176)] than in normal-growth twin pregnancies [13.1% (99/756), p < 0.001, adjusted odds ratio 3.29]. Among sIUGR, the incidence of PE was significantly higher in dichorionic (DC) pregnancies (37.5%, 30/80) than in monochorionic (MC) pregnancies (21.9%, 21/96). The rates of onset at <32 weeks (p = 0.045) and of severe PE (p = 0.025) were higher in sIUGR pregnancies with PE. The systolic blood pressure was also higher in sIUGR pregnancies with PE (152.6 ± 11.8 mmHg) than in normal-growth pregnancies with PE (148.0 ± 8.2 mmHg) (p = 0.042). Additionally, more sIUGR pregnancies were delivered at 32–36 weeks (p = 0.001), and fewer were delivered at ≥36 weeks (p < 0.001). Moreover, the prevalence of severe neonatal asphyxia was higher in sIUGR pregnancies with PE than in normal-growth pregnancies with PE (8.8% versus 2.5%, p = 0.020). Conclusions: sIUGR is associated with increased odds of developing severe PE in twin pregnancies, leading to poorer perinatal outcomes.

Differing Microdeletion Sizes and Breakpoints in Chromosome 7q11.23 in Williams-Beuren Syndrome Detected by Chromosomal Microarray Analysis

Williams-Beuren syndrome (WBS) manifests as supravalvular aortic stenosis, intellectual disability, developmental delay and characteristic facial features. The common WBS deletion region ranges from 1.55 to 1.84 Mb and primarily contains the ELN gene. We analyzed 10 patients diagnosed with 7q11.23 microdeletion syndrome by chromosomal microarray analysis. The clinical features of these patients varied from classic WBS to normal phenotype. All 10 patients exhibited different sizes and breakpoints of chromosome microdeletions ranging from 44 kb to 9.88 Mb. The hemizygosity of the ELN gene was detected in 7 patients, while a normal ELN gene was present in 3 other patients with small deletions. We observed that the phenotypic features of WBS varied in fetuses, children and adults, influenced by the genes, deletion size and breakpoint. Our findings provide more information on the genotype-phenotype correlations of WBS. However, further research is needed to explore the size and breakpoint effect and functions of the genes on chromosome 7q11.23.

Unusual twinning: Additional findings during prenatal diagnosis of twin zygosity by single nucleotide polymorphism (SNP) array

To evaluate the incidence and characteristics of unusual twinning by using single nucleotide polymorphism (SNP) array to identify twin zygosity.

Prenatal diagnosis of posterior fossa anomalies: Additional value of chromosomal microarray analysis in fetuses with cerebellar hypoplasia

To elucidate the relationship between copy number variations (CNVs) detected by high‐resolution chromosomal microarray analysis (CMA) and the type of prenatal posterior fossa anomalies (PFAs), especially cerebellar hypoplasia (CH).

Discordant phenotypes in monozygotic twins with 16p11.2 microdeletions including the SH2B1 gene

A 200∼240 kb SH2B1‐containing deletion region on 16p11.2 is associated with early‐onset obesity and developmental delay. Here, we describe monozygotic twin brothers with discordant clinical presentations. Intrauterine fetal growth restriction was present in both twins. Additionally, twin A exhibited coarctation of aorta, left ventricular noncompaction, atrial septal defect, pericardial effusion, left hydronephrosis, and moderate developmental delay, whereas twin B exhibited single umbilical artery. Chromosome microarray analysis was performed on both twins and their parents. An identical 244 kb microdeletion on 16p11.2 including 9 Refseq genes, including SH2B1, was identified in the twins. The novel findings in monozygotic twins may expand the phenotypic spectrum of 16p11.2 microdeletion. Further studies are needed to strengthen the correlation between genotypes and abnormal clinical features.

Imprinting and Promoter Usage of Insulin-Like Growth Factor II in Twin Discordant Placenta

Case reports from infant twins suggest that abnormal genomic imprinting may be one of the important causes of twin discordance, but it is unknown whether abnormal genomic imprinting occurs in the placenta. Therefore, we sought to determine the relationship between the imprinting of insulin-like growth factor II (IGF-II) in placenta and twin discordance. We analyzed the imprinting and promoter usage of IGF-II in placenta of normal twins (T0 group), weight discordance (T1 group), and phenotype discordance (T2 group). We found the incidence of loss of imprinting (LOI) for IGF-II was higher in the T2 group than that in the T0 and T1 groups, while there was no difference between T0 and T1 groups. The transcripts of promoter 3 were lower in the T2 group than in the T0 and T1 groups, and lower in the twin placenta with LOI than in those with normal imprinting. Our findings indicate that the promoter 3 specific LOI of the IGF-II gene may be closely related with phenotype discordance, not weight discordance.

Chromosomal aberrations and CNVs in twin fetuses with cardiovascular anomalies: Comparison between monochorionic diamniotic and dichorionic diamniotic twins

To investigate the types of cardiovascular anomalies and the results of invasive prenatal diagnosis in twin fetuses.