The prenatal diagnosis of subjects with complete uniparental isodisomy of chromosome 4 (iUPD4) has rarely been reported and poses a great challenge for genetic counseling. In this study, a prenatal case with a high (1 in 58) risk of Down syndrome was diagnosed with iUPD4 by combined chromosomal microarray analysis (CMA), whole exome sequencing (WES) and ultrasound morphology scan. By CMA, a pathogenic copy number variant was not detected; however, a complete maternal iUPD4 was identified in this fetus after analyzing the parental genotype results. To detect potentially autosomal recessive variants, WES was performed. Two missense and two frameshift variants were identified but were predicted with uncertain significance; none of the mutations were definitively associated with congenital abnormality or inherited disease. In addition, a detailed ultrasound morphology scan did not identify any structural abnormalities, facial dysmorphisms or intrauterine growth restriction. The family history was unremarkable. The couple was counseled with the prenatal diagnostic results, and they opted to give birth to the child. No phenotypic abnormalities were observed in this child after the first year of life. This study provides further evidence that iUPD4 can result in a healthy live birth and demonstrates that the combined use of CMA, WES and ultrasound technology provides additional information for the prenatal diagnosis and clinical management of rare UPD events.

Objective: How to reduce the neurodevelopmental toxicity of decabromodiphenyl ether (PBDE-209) remains unclear. This study investigated neurodevelopmental toxicity of PBDE-209 and the protective effects of insulin-like growth factor-1 (IGF-1) Methods: Pregnant Sprague–Dawley rats were treated with PBDE-209 and IGF-1, and the offspring were subjected to the Morris Water Maze test. Hippocampal neurons were cultured with PBDE-209 and IGF-1 or the PI3K inhibitor or MEK inhibitor for cell viability, apoptosis, immunofluorescence, and Western blot assays. Results: Prenatal PBDE-209 exposure impaired the learning and memory ability of rats by delaying the mean latency to the platform compared, whereas prenatal treatment with IGF-1 treatment improved the learning and memory ability. In vitro, treatment of primary cultured hippocampal neural stem cells (H-NSCs) with PBDE-209 reduced cell proliferation and differentiation, but induced apoptosis. In contrast, IGF-1 treatment antagonized the cytotoxic effects of PBDE-209 in H-NSCs in vitro. At the gene level, IGF-1 inhibition of PBDE-209–induced cell cytotoxicity was through the activation of the PI3K/AKT and MEK/ERK signaling pathways in vitro because the effect of IGF-1 was blocked by the AKT inhibitor LY294002 and the ERK1/2 inhibitor PD98059. Conclusion: Prenatal PBDE-209 exposure impaired the learning and memory ability of rats, whereas IGF-1 treatment was able to inhibit the neurodevelopmental toxicity of PBDE-209 by activation of the PI3K/AKT and ERK1/2 cell pathways.

To explore the obstetric and oncological outcomes of CHMCF and to give a beneficial reference for the individualized management of the disease and the timing of pregnancy termination. A 25-year-old primipara was diagnosed with CHMCF at 17 weeks of gestation by prenatal ultrasound. Magnetic resonance imaging, genetics and consanguinity identification testing were performed. There were no serious pregnancy complications. At 38 weeks of gestation, a small-for-gestational-age fetus was delivered by cesarean section, and there was no obvious abnormality in postpartum follow-up. CHMCF belongs to paternal diploid twin pregnancy. Ultrasound and magnetic resonance imaging are important methods for early diagnosis. When the fetal karyotype is normal and there is no obvious pregnancy complication, it is feasible to continue pregnancy, and the incidence of GTN is not significantly increased compared with the termination of pregnancy.

Given that 3-Phosphoinositide-dependent kinase 1 (PDK1) plays a crucial role in malignant biological behaviors of a wide-range of cancers, we further review the influence of PDK1 in breast cancer (BC). First, we describe the power of PDK1 in cellular behaviors and extensively demonstrate the interacting networks of PDK1 via PI3K-dependent/ PI3K-independent pathway. Then we enlighten the roles of PDK1 in carcinogenesis, growth and survival, metastasis, and chemoresistance in BC cells. More important, we sort the current preclinical or clinical trials of PDK1 targeted therapy in BC and find that even though at present no selective PDK1 inhibitor is available for BC therapy, but the combination trials of PDK1 targeted therapy and other agents have demonstrated some benefit. Thus, there is increasing anticipations that PDK1 targeted therapy will have its space in future therapeutic concepts of BC, and we hope to feature PDK1 in BC to the clinic and bring the new promising to patients for targeted therapies.