Yanmin Luo

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.

Placental expression of PHLDA2 in selective intrauterine growth restriction in monozygotic twins

Studies have showed that increase of placental expression of imprinted genes PHLDA2 may have a potential regulatory role in fetal IUGR (intrauterine growth restriction) in singleton. In this study, we investigate the expression level of PHLDA2 in placenta of monozygotic twins (MZT) with selective intrauterine growth restriction (sIUGR) and normal MZT. Both mRNA levels and protein levels of PHLDA2 were significantly increased in placenta sharings of small fetus in cases of sIUGR. Our results suggest upregulated PHLDA2 in placenta may be associated with the pathogenesis of sIUGR.

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.

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 management and outcomes in mirror syndrome associated with twin–twin transfusion syndrome

The aim of this article is to investigate the prevalence, clinical presentation, prenatal management, and prognosis of mirror syndrome associated with twin–twin transfusion syndrome (TTTS) treated by amnioreduction or selective fetocide.

Study on the Imprinting Status of Insulin-Like Growth Factor II (IGF-II) Gene in Villus during 6–10 Gestational Weeks

Objective. To compare the difference of imprinting status of insulin-like growth factor II (IGF-II) gene in villus between normal embryo development group and abnormal embryo development group and to investigate the relationship between karyotype and the imprinting status of IGF-II gene. Methods. A total of 85 pregnant women with singleton pregnancy were divided into two groups: one with abnormal embryo development (n = 38) and the other with normal embryo development (n = 47). Apa I polymorphism of IGF-II gene in chorionic villus was assayed with reverse transcriptase polymerase chain reaction (RT-PCR) and restriction fragment length polymorphism (RFLP). The relationship between chromosomal abnormal karyotype and IGF-II gene imprinting status was analyzed by primary cell culture and G-banding chromosomal karyotype analysis. Results. IGF-II imprinting loss rate was higher in the abnormal embryo development group than the normal embryo development group (44.7% versus 31.6%), but without significant difference (P > .05). The percentage of abnormal chromosomes of chorionic villus in the abnormal embryo development group was 42.5%, in which IGF-II imprinting loss rate reached 64.7%. No abnormal karyotypes were found in the normal embryo development group. However, there was significant difference in IGF-II imprinting loss rate between two groups (P > .05). Conclusion. During weeks 6–10 of gestation, abnormal embryonic development is correlated with chromosomal abnormalities. The imprinting status of IGF-II gene played important roles in embryonic development, and imprinting loss might be related to chromosomal abnormalities.

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.

Chromosome 10q26 deletion syndrome: Two new cases and a review of the literature

The current study presents the cases of two unrelated patients with similar clinical features, including craniofacial anomalies, developmental delay/intellectual disability and cardiac malformations, that are consistent with chromosome 10q26 deletion syndrome. High-resolution single-nucleotide polymorphism analysis revealed that 10q26 terminal deletions were present in these two patients. The locations and sizes of the 10q26 deletions in these two patients were compared with the locations and sizes of 10q26 deletions in 30 patients recorded in the DECIPHER database and 18 patients characterized in previous studies through chromosomal microarray analysis. The clinical features and locations of the 10q26 deletions of these patients were reviewed in an attempt to map or refine a critical region (CR) for phenotypes. Additionally, the association between previously suggested CRs and phenotypic variability was discussed. The current study emphasize that a distal 10q26 terminal deletion with a breakpoint at ~130 Mb may contribute to the common clinical features of 10q26 deletion syndrome.