We present a pregnant woman with a fetus prenatally diagnosed as 46, XY,der(4) t(4;12) (q35.1; q21.2). This defect resulted from the unbalanced segregation of a paternal balanced translocation, t(4;12) (q35.1; q21.2). Prenatal ultrasound revealed borderline ventriculomegaly, a thick nuchal fold, pericardial effusion, arthrogryposis, a single umbilical artery, and micropenis. Fluorescence in situ hybridization (FISH) with whole chromosome painting probe and microarray-based comparative genomic hybridization analysis further confirmed chromosomal gain of terminal 12q. The woman had her pregnancy terminated at 20 weeks of gestational age. When compared with previously reported cases, the proband had characteristics common to the phenotypes of partial trisomy 12q, including an abnormal facial appearance and multiple anomalies. Additionally, this case had previously unreported phenotypes, such as arthrogryposis, a single umbilical artery, and a micropenis. Regarding the outcome of partial trisomy 12q, the fetuses carrying trisomies distal to 12q24 have a good chance of extended postnatal survival. In contrast, the cases with trisomies involving a larger amount of 12q likely die prenatally or within a few days after birth.
To test the hypothesis that human amniotic fluid mesenchymal stem cells contain a unique epigenetic signature in imprinting centers of H19, SNRPN, and KCNQ1OT1 during in vitro cell culture.By bisulfite genomic sequencing, we analyzed the imprinting centers of three imprinted genes (including H19, SNRPN, and KCNQ1OT/) in a total of six single-cell clones of human amniotic fluid mesenchymal stem cells at cell passages 7, 8, 9, and 10 during in vitro cell culture.The imprinting centers of H19 and KCNQ1OT1 showed hypermethylation at passage 7 in all single-cell clones of human amniotic fluid mesenchymal stem cells, and there was no significant change in DNA methylation patterns during in vitro cell culture. The imprinting centers of SNRPN showed variable methylation patterns at passage 7 in six single-cell clones, and DNA methylation patterns varied during in vitro cell culture from passages 8 to 10.In conclusion, human amniotic fluid mesenchymal stem cells contain a unique epigenetic signature during in vitro cell culture. H19 and KCNQ1OT1 possessed a substantial degree of hypermethylation status, and variable DNA methylation patterns of SNRPN was observed during in vitro cell culture of human amniotic fluid mesenchymal stem cells. Our results urge further understanding of epigenetic status of human amniotic fluid mesenchymal stem cells before it is applied in cell replacement therapy.
Transcutaneous electrical nerve stimulation (TENS) is one of the non-pharmacological means of pain relief for labor and delivery. We aimed to investigate the efficacy and safety of TENS on specific acupuncture points for reducing pain in the first stage of labor. In this double-blind, placebo-controlled trial, we randomly assigned healthy full-term parturients in active phase of first-stage labor to either TENS on four acupuncture points (Hegu [Li 4] and Sanyinjiao [Sp 6]) (n=52) or the TENS placebo (n=53). Visual analogue scale (VAS) was used to assess pain before and 30 and 60 min after treatment. The primary outcome was the rate of VAS score decrease 3 in each group. A questionnaire was given at 24h post-partum to evaluate the satisfaction of pain relieving method and the willingness to have the same treatment again. Mode of delivery and neonatal effect were measured as secondary outcome. One hundred women were eligible for analysis. TENS group experienced VAS score reduction 3 significantly more common than the TENS placebo group (31/50 [62%] vs 7/50 [14%], P<0.001). Willingness of using the same analgesic method for a future childbirth was also significantly different (TENS: 48/50 [96%] vs TENS placebo: 33/50 [66%], P<0.001). Operative delivery was increased in the TENS group (12/50 [24%] vs 4/50 [8%], P=0.05), but the neonatal outcomes were not different. The application of TENS on specific acupuncture points could be a non-invasive adjunct for pain relief in the first stage of labor.
A complete hydatidiform mole (CHM) is an abnormal pregnancy with hyperproliferative vesicular trophoblast and no fetal development. Most CHM are sporadic and androgenetic, but recurrent HM have biparental inheritance (BiHM) with disrupted DNA methylation at differentially methylated regions (DMRs) of imprinted loci. Some women with recurrent BiHM have mutations in the NLRP7 gene on chromosome 19q13.42. Using bisulfite genomic sequencing at eight imprinted DMRs on DNA from two BiHMs, we found a pattern of failure to acquire or maintain DNA methylation at DMRs (PEG3, SNRPN, KCNQ1OT1, GNAS exon 1A) that normally acquire CpG methylation during oogenesis, but not at H19, which acquires CpG methylation during spermatogenesis. Secondary imprints at the GNAS locus showed variable abnormal patterns with both gain and loss of CpG methylation. We found novel missense and splice-site mutations in NLRP7 in women with non-familial recurrent BiHM. We identified and characterized a homozygous intragenic tandem duplication including exons 2 through 5 of NLRP7 that results in a predicted truncated protein in affected women of three unrelated Egyptian kindreds, suggesting a founder effect. Our findings firmly establish that NLRP7 mutations are a major cause of BiHM and confirm presence of a complex pattern of imprinting abnormalities in BiHM tissues.
Microarray analyses of transcriptomes have been used to characterize mesenchymal stem cells (MSCs) of various origins. MicroRNAs (miRNAs) are short, nonprotein-coding RNAs involved in post-transcriptional gene inhibition in a variety of tissues, including cancer cells and MSCs. This study has integrated the use of miRNA and mRNA expression profiles to analyze human MSCs derived from Wharton's jelly (WJ) of the umbilical cord, milk teeth (MT), and adult wisdom teeth (AT). Because both miRNA and mRNA expression in MT and AT MSCs were so similar, they were combined together as tooth MSCs for comparison with WJ MSCs. Twenty-five genes that were up-regulated in tooth MSCs and 41 genes that were up-regulated in WJ MSCs were identified by cross-correlating miRNA and mRNA profiles. Functional network analysis show that tooth MSCs signature genes, represented by SATB2 and TNFRSF11B, are involved in ossification, bone development, and actin cytoskeleton organization. In addition, 2 upregulated genes of tooth MSCs-NEDD4 and EMP1-have been shown to be involved in neuroectodermal differentiation. The signature genes of WJ MSCs, represented by KAL1 and PAPPA, are involved in tissue development, regulation of cell differentiation, and bone morphogenetic protein signaling pathways. In conclusion, the combined interrogation of miRNA and mRNA expression profiles in this study proved useful in extracting reliable results from a genome-wide comparison of multiple types of MSCs. Subsequent functional network analysis provided further functional insights about these MSCs.
Abstract Labor and its associated pain are thought to have unique impacts on parturient women. The goal of this study was to investigate the effects of labor and associated pain on differential gene expression profiles in the maternal, fetal, and placental compartments. We used microarrays to analyze maternal blood (MB), fetal cord blood (CB), and placental tissue samples in pregnant women after term vaginal deliveries (laboring group) and in term pregnant women after scheduled Ceasarean sections (nonlaboring group). The upregulated genes in the MB of the laboring group are involved in cytokine and nuclear factor‐kappa B signaling pathways, regulation of the networks of toll‐like receptor 4, and suppressor of cytokine signaling 3. Upregulated genes in the CB of the laboring group are involved in responding to stress and stimuli by regulating the network genes of the T‐cell receptor beta locus and the FK506 binding protein 8. Differentially expressed genes in the placenta of the laboring group are involved in nitric oxide transport, gas transport, response to hydrostatic pressure, oxygen transport, acute phase responses, and the tumor necrosis factor‐mediated signaling pathway, which are important during the transient hypoxemia and hypoperfusion that occur in the placenta during uterine contractions. Interestingly, few of the genes exhibited simultaneous changes in all three compartments, indicating that different pathways and complex interactions may be involved in human labor. In conclusion, human labor and its associated pain elicit unique gene regulatory changes in MB, placenta, and CB.
Discordance of fetal genotype or phenotype in a monozygotic twin pregnancy is rare.In case 1, a 28-year-old woman at 15 weeks' gestation was found to have a dichorionic twin pregnancy with 1 fetus affected with hydrop fetalis. The result of chromosomal study showed that the structurally normal fetus was 46,XY and that the hydropic fetus was 45,X. One week after selective termination of the hydropic fetus at 19 weeks' gestation, the cotwin died in utero. In case 2, a 30-year-old woman at 20 weeks' gestation, was found to have a monochorionic twin pregnancy with 1 fetus presenting with omphalocele. The result of chromosomal study showed that both fetuses were 46,XX. The fetus with omphalocele died in utero at 29 weeks' gestation, and the normal cotwin was delivered later due to fetal distress. Analysis by short tandem repeat markers in both cases indicated that they were monozygotic twins.These cases emphasize the importance of zygosity/chorionicity identification in twin pregnancy even though discordance of fetal genotype or phenotype was found. In monozygotic monochorionic twins, the normal cotwin is at risk for an adverse fetal outcome after 1 spontaneous intrauterine fetal death or selective termination. In monozygotic dichorionic twins, the risk of intrauterine fetal demise of the cotwin after selective termination still exists.
Karyotype analysis on amniotic fluid samples or chorionic villi has limited resolution and there is a delay between sampling and results. Therefore, invasive prenatal diagnosis has been reserved for pregnancies that are at increased risk for a defined genetic disorder, or for common aneuploidies found in liveborns. However, more than 70 disorders are now known to be associated with birth defects or developmental problems that are caused by deletion or duplication of a small chromosomal segment. These conditions and aneuploidies can be detected by array-based comparative genomic hybridization (CGH), which can evaluate the copy number of thousands of genomic regions simultaneously in a single assay. We review current knowledge on benign and pathological genomic copy number variants, principles of array CGH and its use for discovery and diagnosis of genetic diseases. Array CGH has already revolutionized genetic diagnosis in children and adults and is being used increasingly for prenatal diagnosis.
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